bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased heart rate accelerates norepinephrine washout from normal myocardium
Authors: Henning R. J. , Cheng J. , Bhat A. M. , Levy M. N.
Published: December 2017

We determined whether a change in heart rate affected the decay of the ventricular inotropic response to sympathetic stimulation in an experimental group and in a control group of anesthetized dogs. We induced complete heart block in each animal and paced the ventricles at rates of 90, 120, and 150 min-1 during two observation periods. In the experimental group, desipramine hydrochloride was given during the second period to block the neuronal uptake mechanism. The control animals did not receive desipramine during either period. The time required for the ventricular inotropic response to decay by 50% after cessation of a 2-min train of sympathetic stimulation was used as an index of the rate of norepinephrine washout from the myocardial interstitium. As we increased the pacing rate over the range of 90-150 min-1 in the experimental group, the mean decay half times (+/- SE) decreased by 36 +/- 4% (P less than 0.001) before desipramine and by 26 +/- 6% (P less than 0.001) in the presence of desipramine. These decrements in the decay half times were not significantly different from each other. The mean decay half times decreased by 36 +/- 4% (P less than 0.001) in the control dogs; the effects did not change appreciably from the first to the second observation period. We conclude that an increase in pacing frequency facilitates the washout of norepinephrine from the ventricular myocardium; this facilitation is equally pronounced regardless of whether the neuronal uptake mechanism is intact or suppressed.
Effects of atriopeptin III on isolated mesenteric resistance vessels from SHR and WKY
Authors: Cauvin C. , Tejerina M. , van Breemen C.
Published: December 2017

The effects of atriopeptin III (AP III) were determined on agonist-induced [i.e., 10(-4) M norepinephrine (NE)] and depolarization-induced (80 mM K+) contractions of isolated mesenteric resistance vessels (ID approximately 100 microns) from spontaneously hypertensive rats (SHR) and from normotensive control Wistar-Kyoto (WKY) rats. The vessels from both groups, when activated by 80 mM K+, were unaffected by AP III. However, activation of WKY vessels by 10(-4) M NE (both phasic and tonic contraction) was inhibited quite effectively and potently by AP III, whereas that in SHR vessels was much less inhibited. In the WKY rat vessels, the concentration of AP III that inhibited contraction by 50% for NE-induced phasic tension was 3.1 +/- 1.3 nM, whereas in SHR vessels it was nearly 1 microM. Comparison of AP III inhibition of NE-induced phasic tension to that at 5 min of activation (tonic tension) indicated that the tonic contractions were less sensitive to AP III than the phasic contractions in the vessels from both strains. A similar experiment indicated that AP III was a potent inhibitor of agonist-induced activation in a human renal resistance vessel (ID 125 microns) and that this vessel depended virtually completely on extracellular Ca2+ for NE-induced contraction. These studies contrast with earlier reports (1, 30) that similar peptides inhibited tension only in rat renal resistance vessels and not in resistance vessels from other vascular beds. The decreased sensitivity and efficacy of AP III in inhibiting tension in SHR compared with WKY mesenteric resistance vessels is discussed in the context of the etiology of spontaneous hypertension.
Atrial natriuretic factor in dogs with one-kidney, one-clip Goldblatt hypertension
Authors: Verburg K. M. , Freeman R. H. , Villarreal D. , Brands M. W.
Published: December 2017

The temporal changes in the plasma concentration of immunoreactive atrial natriuretic factor (ANF) were studied in dogs (n = 5) before and after renal artery constriction to produce one-kidney, one-clip renovascular hypertension. Three days after renal artery constriction, circulating ANF increased from 34 +/- 7 to 344 +/- 129 pg/ml (P less than 0.05) in association with a 38-mmHg elevation of mean arterial pressure and increases in plasma renin and aldosterone levels. Plasma renin and aldosterone remained elevated for 9 days after renal artery constriction. Arterial pressure stabilized at this elevated level of 35-40 mmHg above base line for the duration of the 4 wk after renal artery constriction. Right atrial filling pressure did not change significantly (P greater than 0.05) after constriction of the renal artery. This observation suggests that volume expansion with right atrial distention is not the only stimulus for release of ANF in these hypertensive dogs. Plasma ANF remained significantly elevated above base-line levels for 7 days postconstriction even though a twofold decrease from the maximal response of 344 +/- 129 pg/ml on day 3 to 168 +/- 48 pg/ml on day 7 was observed during this same time interval. Plasma ANF continued to decrease toward prehypertensive levels throughout the remainder of the established phase of the hypertension lasting an additional 21 days of observation. The mechanisms for this observed pattern of plasma ANF are unclear but may involve changes in left atrial distention and stretch as a stimulus for hormone secretion with progression of the hypertension.
An electronic, negative feedback device to control arterial pressure
Authors: Pardini B. J. , Lund D. D. , Wurster Robert D. , Anderson R. H.
Published: December 2017

Page H191: B. J. Pardini, D. D. Lund, Robert D. Wurster, and R. H. Anderson. “An electronic, negative feedback device to control arterial pressure.” The received dates should read: “Received 5 June 1987; accepted in final form 27 August 1987.
Phase-locked rhythms in periodically stimulated heart cell aggregates
Authors: Guevara M. R. , Shrier A. , Glass L.
Published: December 2017

We have studied the effect of injecting a periodic train of current pulses into spontaneously beating aggregates of embryonic chick ventricular heart cells. Over a range of stimulation frequencies around the intrinsic frequency of an aggregate we find one action potential for each stimulus with a fixed latency from each stimulus to the subsequent action potential. For a stimulation frequency higher (lower) than the intrinsic frequency, this corresponds to overdrive (underdrive). At high frequencies of stimulation dropped beats occur leading to complex rhythms analogous to various Wenckebach rhythms observed clinically. At higher stimulation frequencies one can obtain a complete suppression of action potential generation. At low frequencies of stimulation, there are rhythms containing escape beats. Almost every rhythm seen bears a striking resemblance to some cardiac arrhythmia. We present a simple classification scheme that predicts the order of appearance of all the classes of rhythms experimentally observed as one changes the stimulation frequency. We propose that this scheme can be used generally to describe the behavior of other biological oscillators.
Vascular relaxation and cGMP in hypertension
Authors: Otsuka Y. , DiPiero A. , Hirt E. , Brennaman B. , Lockette W.
Published: December 2017

Isolated aortas from hypertensive rats have a decreased relaxation response to acetylcholine chloride (ACh), the calcium ionophore A23187, and sodium nitroprusside (SNP). Since the vascular relaxation responses to these vasodilators may be a result of increases in guanosine 3',5'-cyclic monophosphate (cGMP), we measured the cGMP response to these agents in isolated aortas from normotensive rats and rats with either mineralocorticoid-induced hypertension (DOCA), renovascular hypertension (1K1C), or coarctation-induced hypertension (Coarc). The aortas from the hypertensive rats had decreased basal levels of cGMP and attenuated increases in cGMP in response to ACh and A23187. Rises in cGMP in response to SNP were also attenuated in aortas from the hypertensive rats, even at concentrations that induced maximum relaxation of blood vessels from normotensive and hypertensive rats. The relaxation responses to atrial natriuretic factor (ANF) and the cGMP generated in isolated aortas by ANF were attenuated in hypertension. Removal of the endothelium markedly attenuated cGMP generation in response to ANF in vessels from normotensive and Coarc rats, but the relaxation responses to ANF were unaltered in vessels after the removal of the endothelium. The reversal of experimentally induced hypertension was associated with increases in cGMP levels following exposure of the isolated vessels to ACh. Also, vessels treated with methylene blue relaxed in response to SNP despite inhibition of cGMP accumulation. The decreased relaxation response to endothelium-dependent vasodilators is accompanied by decreases in cGMP accumulation; the decreased vascular cGMP content in response to endothelium-dependent vasodilators is not due to increases in phosphodiesterase activity of vascular smooth muscle; and SNP may relax blood vessels through “cGMP-dependent” and “cGMP-independent” mechanisms.
Initial equilibration of albumin in rabbit hindpaw skin and lymph
Authors: Powers M. R. , Wallace J. R. , Bell D. R.
Published: December 2017

We compared initial plasma to extravascular and plasma to lymph equilibrations of 125I-labeled rabbit albumin in hindpaw heelskin of anesthetized rabbits during control conditions, increased venous pressure (IVP), and intra-arterial infusions of papaverine or bradykinin. Plasma tracer concentrations were maintained constant during the experiments. Control prenodal lymph specific activity relative to plasma specific activity (L*/P*) was significantly greater (P less than 0.01) than extravascular specific activity relative to plasma specific activity (M/P) following 3, 5.5, and 11 h of tracer infusion. Papaverine increased lymph flow and lymph albumin flux (LCL) 2.4-fold, without significantly changing the extravascular albumin mass (MA). IVP increased LCL 2.5-fold and decreased MA 25%. L*/P* at 3 h was twice control following papaverine. M*/P* at 3 h was not significantly affected by papaverine or IVP. Bradykinin increased LCL 10-fold and MA 2.3-fold. L*/P* and M*/P* were 3.1 and 4.3 times control, respectively. The data are consistent with extravascular albumin distributing into two pools that equilibrate with plasma at different rates. Papaverine and IVP affect the faster pool, whereas bradykinin affects both pools.
Differentiation of beta 1- and beta 2-adrenoceptor-mediated effects in humans
Authors: Brodde O. E. , Daul A. , Wellstein A. , Palm D. , Michel M. C. , Beckeringh J. J.
Published: December 2017

To differentiate beta 1- and beta 2-adrenoceptor-mediated effects in humans, we studied the effects of a 2-wk treatment of 12 male volunteers with the selective beta 1-adrenoceptor antagonist bisoprolol (1 x 10 mg/day) and the beta 2-selective antagonist ICI 118,551 (3 x 25 mg/day) on lymphocyte beta 2-adrenoceptor density and responsiveness [10 microM l-isoproterenol (IPN) evoked adenosine 3',5'-cyclic monophosphate (cAMP) increase] as well as on exercise- and IPN-induced changes in lymphocyte beta 2-adrenoceptor density, blood pressure, heart rate, and plasma norepinephrine levels. ICI 118,551 administration increased lymphocyte beta 2-adrenoceptor density and responsiveness by approximately 50%, whereas bisoprolol had no effect. Dynamic exercise on a bicycle and infusion of graded doses of IPN led to an approximately 100% increase in lymphocyte beta 2-adrenoceptor density; this was abolished by ICI 118,551 but not affected by bisoprolol. ICI 118,551 markedly attenuated IPN-induced decrease in diastolic blood pressure but did not affect increase in systolic blood pressure, whereas bisoprolol had opposite effects. The IPN-induced increase in heart rate, however, was antagonized by both bisoprolol and (to a greater extent) ICI 118,551. Finally, ICI 118,551 completely abolished the IPN-induced increase in plasma norepinephrine levels, whereas bisoprolol had no effect. These results indicate that bisoprolol and ICI 118,551 are suitable tools to differentiate in humans beta 1- and beta 2-adrenoceptor-mediated effects.
High-intensity exercise training increases vascular transport capacity of rat hindquarters
Authors: Sexton W. L. , Korthuis R. J. , Laughlin M. H.
Published: December 2017

The purpose of this study was to determine whether high-intensity exercise training increases the vascular flow capacity and capillary exchange capacity in isolated rat hindquarters. One group of 20 male Sprague-Dawley rats underwent six bouts of alternating running (2.5 min) and recovery (4.5 min), 5 days/wk at 60 m/min on a 15% grade for 6-10 wk (high-intensity exercise training), while a second group of 20 rats was cage confined (sedentary controls). Experiments were conducted in isolated, maximally dilated (papaverine) hindquarters perfused with an artificial plasma consisting of a Tyrode's solution containing 5 g/100 ml albumin. Vascular flow capacity was evaluated by measuring perfusate flow rate at four different perfusion pressures. Capillary exchange capacity was evaluated by measuring the capillary filtration coefficient. The efficacy of training was demonstrated by significant increases in succinate dehydrogenase activity in the white vastus lateralis and vastus intermedius muscles. Total hindquarter flow capacity was elevated 50-100% in the trained rats. This increased flow capacity was associated with an increase in the capillary filtration coefficient in the maximally vasodilated hindquarters, thus suggesting that the capillary exchange capacity was increased with high-speed exercise training. These results suggest that the vascular transport capacity in rat hindquarter muscles is significantly increased by high-intensity exercise training.
Left ventricular function during chronic endotoxemia in swine
Authors: Lee K. , van der Zee H. , Dziuban S. W. , Luhmann K. , Goldfarb R. D.
Published: December 2017

Cardiac performance was studied in 15 chronically instrumented awake pigs during chronic endotoxemia (CET) induced by intravenous infusion of low doses of endotoxin. We sought to test the hypothesis that left ventricular inotropic state was depressed during the stage of chronic endotoxemia when cardiac output, heart rate, and left ventricular systolic pressures are elevated, termed "hyperdynamic sepsis". Left ventricular pressure, internal short axis diameter (SAX), pulmonary artery blood flow, and electrocardiogram were recorded. After initial surgical preparation, each pig was observed for 7-10 days to measure representative basal values. Each pig was then reoperated on day 10 to implant an endotoxin-loaded osmotic pump whose output, infused Salmonella enteritidis endotoxin at a rate calculated to be 10 micrograms.kg-1.h-1 for up to 7 days. Cardiac performance was monitored by measuring dP/dt, heart rate, stroke volume, end-diastolic diameter, percent change in diameter, and the slope of the end-systolic pressure diameter relationship (ESPDR). Data from the basal days were pooled and compared with the data obtained each day of CET by two-way analysis of variance. Ten of 15 pigs survived more than 2 days of CET; 5 died before the morning of the second CET day. The surviving pigs demonstrated elevated systolic pressures, left ventricular maximum rate of pressure development (+dP/dtmax and -dP/dtmax), heart rates, and cardiac output. However, both ESPDR and percent SAX shortening were significantly depressed during both CET days. We conclude that cardiac inotropic state is depressed during hyperdynamic sepsis as indicated by the load-independent parameter ESPDR and confirmed by depressed percent SAX shortening.
Adenosine handling in interstitia of cremaster muscle studied by bioassay
Authors: Mohrman D. E.
Published: December 2017

We used video-microscopic techniques to study responses of rat cremaster muscle arterioles to adenosine (ADO) placed in a bathing solution in an effort to determine 1) the sensitivity of these vessels to local interstitial ADO concentration and 2) the parameters of interstitial adenosine handling. Two vessels, located at different depths (approximately 40 and 115 microns) below the surface of the tissue, were studied simultaneously. Invariably, a higher bath ADO concentration was required to induce vasodilation in the deeper vessel; the concentration required for 50% dilation response (EC50) for ADO dilation increased at an average of 1.8 +/- 0.2 log10 U/100 microns of depth into the tissue. This result was shown to be due to a standing gradient in interstitial ADO concentration. By extrapolating results to the tissue surface, we estimate that the EC50 for arteriolar dilation to local interstitial ADO is approximately 0.1 microM. The steepness of the tissue ADO gradient indicates that the rate constant for interstitial ADO loss is near 0.24/s. The gradients for nonmetabolizable adenosine analogues were less than 1/10th as steep as that for ADO itself. Qualitatively similar results were obtained from experiments on hamster cremaster muscle preparations.
Adenosine deaminase attenuates norepinephrine-induced coronary functional hyperemia
Authors: Downey H. F. , Merrill G. F. , Yonekura S. , Watanabe N. , Jones C. E.
Published: December 2017

Responses to norepinephrine (NE) before and after treatment with adenosine deaminase (ADA) were examined in anesthetized dogs. In four dogs repeatable changes in coronary blood flow, myocardial oxygen extraction and consumption, left ventricular +dP/dtmax, and heart rate (HR) were demonstrated during two successive intracoronary infusions of 0.13 micrograms.kg-1.min-1 NE. In eight dogs, the NE-induced hyperemia was decreased from +150 to +67%, the change in myocardial oxygen consumption (MVo2) was attenuated from +177 to +101% by ADA, and the increase in HR was reduced from +28 to +16%. In six dogs, the increase in HR caused by NE before ADA was maintained after ADA by atrial pacing. The NE-induced hyperemia and the increase in MVo2 were again decreased by ADA. Similar results were observed in 12 other dogs with hearts paced at a constant, elevated rate during control as well as during both infusions of NE. In all groups, the O2 extraction response to increased MVo2 increased and the flow response decreased after ADA. In six dogs nitroprusside was infused during NE after ADA. When coronary flow was restored to the same level observed before deaminase, MVo2 was not diminished. These results support a role for adenosine in the coronary functional hyperemia accompanying NE activation of the canine myocardium.
Cardiovascular effects of AVP and ANG in experimental pulmonic stenosis in rats
Authors: Riegger G. A. , Albert M. , Kochsiek K.
Published: December 2017

Our objectives were to examine the role of vasopressin and renin in the regulation of peripheral vascular tone in an animal model of right ventricular failure due to chronic (10 wk) pulmonic stenosis. We tested in chronically instrumented conscious control rats and in rats with pulmonic stenosis on a normal and a high-sodium diet both vasoconstrictor systems by applying specific inhibitors. The rats with pulmonic stenosis showed significant hemodynamic changes, a hypertrophy of the right ventricle, increased levels of plasma renin concentration, and inappropriately elevated plasma levels of vasopressin in comparison to control animals. Plasma renin concentration was suppressed in the sodium-loaded controls. After the administration of a specific inhibitor of the vascular receptors of arginine vasopressin [30 micrograms, d(CH2)5Tyr(Me)AVP], we found no hemodynamic changes in control rats on the normal diet, a reduction of mean arterial pressure in the sodium-loaded controls (4 +/- 4 mmHg; P less than 0.005), and in the animals with pulmonic stenosis and normal sodium intake (5 +/- 5 mmHg; P less than 0.001) and high-salt diet (6 +/- 7 mmHg; P less than 0.02). Intravenous bolus injection of teprotide (1 mg/kg) resulted in a decrease of mean arterial pressure in the control group (normal diet) of 9 +/- 8 mmHg (P less than 0.005). The fall of blood pressure (22 +/- 10 mmHg; P less than 0.001) in the rats with pulmonic stenosis was significantly greater (P less than 0.01) and was strongly related to plasma renin concentration. Therefore, vasopressin and the renin-angiotensin system contribute to an increase of peripheral vascular tone in chronic pulmonic stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Cholinergic neurotransmission in human corpus cavernosum. II. Acetylcholine synthesis
Authors: Blanco R. , Saenz de Tejada I. , Goldstein I. , Krane R. J. , Wotiz H. H. , Cohen R. A.
Published: December 2017

Physiological and histochemical evidence indicates that cholinergic nerves may participate in mediating penile erection. Acetylcholine synthesis and release was studied in isolated human corporal tissue. Human corpus cavernosum incubated with [3H )choline accumulated [3H]choline and synthesized [3H]acetylcholine in a concentration-dependent manner. [3H]Acetylcholine accumulation by the tissue was inhibited by hemicholinium-3, a specific antagonist of the high-affinity choline transport in cholinergic nerves. Transmural electrical field stimulation caused release of [3H]acetylcholine which was significantly diminished by inhibiting neurotransmission with calcium-free physiological salt solution or tetrodotoxin. These observations provide biochemical and physiological evidence for the existence of cholinergic innervation in human corpus cavernosum.
Influence of risk area size and location on native collateral resistance and ischemic zone perfusion
Authors: Gumm D. C. , Cooper S. M. , Thompson S. B. , Marcus M. L. , Harrison D. G.
Published: December 2017

To examine the effect of risk area size on collateral resistance and ischemic region perfusion, we produced different sized risk areas by occluding either the left anterior descending (LAD) or the circumflex (Cx) coronary artery at different sites. The most proximal occlusion of the LAD and Cx produced risk areas of 43 +/- 5 and 36 +/- 2% of left ventricular (LV) mass, respectively, whereas distal LAD and Cx occlusions produced risk areas of 13 +/- 2 and 17 +/- 2% of LV weight, respectively. Although total collateral flow was highest to the largest risk areas, collateral flow per 100 g of ischemic myocardium was 80% higher to the small LAD risk area compared with the large LAD risk area and 43% higher to the small Cx risk area compared with the large Cx risk area. Collateral resistance, calculated from the transcollateral pressure and perfusion per 100 g of myocardium was significantly lower in the small risk areas than in the large ones. We examined the effect of risk area location on collateral perfusion and resistance. Small risk areas (6% LV mass) were created near the base and at the apex of 10 hearts. Collateral flow per 100 g was 60% higher and transcollateral resistance per 100 g 50% lower at the apex than at the base. These experiments show that collateral resistance is influenced both by ischemic region size and location. Small risk areas receive more collateral flow per mass of tissue than large risk areas, and apical risk areas receive greater quantities of collateral flow than those located at the base.(ABSTRACT TRUNCATED AT 250 WORDS)
fMLP provokes coronary vasoconstriction and myocardial ischemia in rabbits
Authors: Gillespie M. N. , Booth D. C. , Friedman B. J. , Cunningham M. R. , Jay M. , DeMaria A. N.
Published: December 2017

Recent pathological studies of coronary arteries from humans with suspected coronary spasm have revealed an augmented intramural burden of inflammatory cells. To test the hypothesis that inappropriate activation of inflammatory cells participates in the evolution of coronary vasospasm, the present experiments employed a newly developed coronary arteriographic technique for use in pentobarbital-anesthetized rabbits to evaluate the coronary vasomotor actions of the nonselective inflammatory cell stimulant, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). In 10 of 10 animals, selective left intracoronary injection of 200 ng fMLP evoked profound left coronary narrowing accompanied in all cases by ST segment deviation and dysrhythmias. Thallium-201 scintigraphy demonstrated hypoperfusion of the left ventricular free wall and septum supplied by the spastic coronary artery. The fMLP-induced epicardial vaso-constriction, ischemic electrocardiogram (ECG) changes, and thallium perfusion defects were reversed by intravenous nitroglycerin. Neither the right coronary artery nor its distribution were influenced by left coronary injection of fMLP. Additional experiments in isolated, salt solution-perfused rabbit hearts demonstrated that fMLP failed to exert direct coronary vasoconstrictor effects. These observations indicate that the non-selective inflammatory cell stimulant, fMLP, provokes arteriographically demonstrable coronary spasm with attendant myocardial hypoperfusion and ischemic ECG changes in anesthetized rabbits. Such a model may be useful in exploring the dynamic role of inflammatory cells in development of coronary spasm.
Effect of hypoxia on lung lymph flow in newborn lambs with left atrial hypertension
Authors: Raj J. U. , Hazinski T. A. , Bland R. D.
Published: December 2017

To determine the effect of left atrial hypertension on the vascular response to hypoxia in the newborn lung, we measured pulmonary artery and left atrial pressures, lung blood flow and lymph flow, and concentrations of protein in lymph and plasma of 13 lambs that spontaneously breathed air for 2-6 h (control period), followed by 8-11% O2 mixed with 3-5% CO2 and N2 for 2-4 h (experimental period). In eight studies, the lambs were made hypoxic first, after which we elevated their left atrial pressure by 10-12 Torr for 2-3 h. In 10 additional studies, we reversed the sequence by raising left atrial pressure first followed by addition of hypoxia. In lambs with normal left atrial pressure, alveolar hypoxia increased both pulmonary blood flow and lymph flow, with an associated reduction in lymph-to-plasma protein ratio (L/P). When left atrial pressure was increased in the presence of hypoxia, lymph flow increased by a small amount and L/P decreased further. In lambs with preexisting left atrial pressure elevation, addition of alveolar hypoxia increased both blood flow and lymph flow with no significant change in L/P. These results suggest that in newborn lambs with normal left atrial pressure, alveolar hypoxia increases lung lymph flow mainly by increasing microvascular filtration pressure, whereas in lambs with elevated left atrial pressure, hypoxia increases lymph flow by another mechanism, perhaps by increasing the perfused surface area for fluid filtration.
Coronary hemodynamic responses during local hemodilution in canine hearts
Authors: Crystal G. J.
Published: December 2017

To evaluate the effect of hemodilution per se on coronary hemodynamics, experiments were performed in 36 anesthetized, open-chest dogs whose left anterior descending coronary artery (LAD) was perfused selectively with either normal arterial blood or arterial blood diluted with lactated Ringer solution. LAD blood flow (CBF) was measured with an electromagnetic flowmeter and its transmural distribution assessed with 15-microns radioactive microspheres. LAD perfusion pressure was set at the normal level (approximately 100 mmHg) or at 50% of that level to simulate coronary insufficiency. Dilator reserve capacity was calculated from ratio of reactive hyperemic peak flow following release of 90-s occlusion to control (preocclusion) flow. Systemic hemodynamic parameters were maintained near control values during coronary hemodilution. With perfusion pressure normal, graded hemodilution caused progressive, transmurally uniform increases in CBF that showed a nonlinear relationship to inflow hematocrit. Increased peak reactive hyperemic flow and decreased dilator reserve ratio indicated that both reduced viscosity and vasodilation contributed to increased CBF during hemodilution. Hypotension alone reduced CBF, with greater effect in the subendocardium. Additional hemodilution returned CBF to normotensive value, but relative subendocardial hypoperfusion persisted. The present study provides fundamental information on effects of hemodilution on coronary hemodynamics without the systemic responses that complicated previous studies utilizing whole body exchange transfusions.
Ventricular preload alters intravascular and extravascular resistances of coronary collaterals
Authors: Conway R. S. , Kirk E. S. , Eng C.
Published: December 2017

Coronary collateral blood flow is determined by both the collateral vessel resistance and a waterfall mechanism. The aim of this study was to determine which of these two mechanisms predominates during alteration of ventricular preload. The left anterior descending coronary artery of 12 anesthetized dogs was cannulated, and the distal vasculature was completely embolized with 25-micron diameter microspheres. Retrograde blood flow (RBF) was collected when the cannula was opened to the atmosphere, and the outflow tubing height was adjusted to provide a variable back pressure. RBF is back pressure-dependent at higher back pressures, and the slope in this region of the constructed pressure-flow relationship determines the collateral conductance. The transition point between the back pressure-dependent and a back pressure-independent region indicates a waterfall pressure impinging on the collateral vessels. At a left ventricular diastolic pressure of 9.3 mmHg, mean RBF, collateral conductance, and the collateral waterfall pressure were 7.3 ml/min, 0.175 ml.min-1.mmHg-1, and 30.1 mmHg, respectively. Corresponding values when preload was reduced to 3.5 mmHg were 9.3 ml/min, 0.186 ml.min-1.mmHg-1, and 23.7 mmHg, all changes being significant. Mean contribution to the overall increase in RBF was 0.5 ml/min for the conductance and 1.2 ml/min for the waterfall mechanism (P less than 0.05), or 29 and 71%, respectively. The results indicate that the extravascular resistance mechanism mediates the collateral flow response to a greater degree than the intravascular resistance during variations in preload. The increase in slope of the conductance portion of the relationship was not accompanied by a concomitant increase in slope of the back pressure-independent region. These data further support a collateral waterfall, and not collateral vessel compliance, as the basis for the back pressure-independent portion of the pressure-flow relationship.
Measurement of hydroxy-conjugated dienes after ischemia-reperfusion in canine skeletal muscle
Authors: Lindsay T. , Walker P. M. , Mickle D. A. , Romaschin A. D.
Published: December 2017

Recent studies have suggested that oxygen-derived free radicals are involved in the reperfusion injury of ischemic skeletal muscle. Although postischemic necrosis and increased vascular permeability have been attenuated with the addition of free radical scavengers, no unequivocal chemical evidence for free radical injury in skeletal muscle is available. The purpose of this study was to identify products of free radical-mediated membrane injury by isolation of lipid oxidation products (hydroxy-conjugated dienes) from postischemic skeletal muscle. The bilateral canine gracilis muscle model was used, and in each pair one muscle was exposed to 3 and the other to 5 h of normothermic ischemia. Muscle biopsies were taken before and at end ischemia, as well as during the first 3 h of reperfusion. Phospholipids were extracted from the muscle biopsies and the fatty acids hydrolyzed from the 2 position. After methylation, the oxidized fatty acid esters were separated by high-performance liquid chromatography. Hydroxy diene peaks absorbing at 235 nm were collected and subjected to gas chromatography-mass spectrometry (GC-MS) for positive structural identification. No significant increase in the level of conjugated dienes occurred during ischemia. Significant increases, however, were detected during the period of reperfusion, although the time when peak levels were achieved varied between animals. The cumulative sum of dienes produced during reperfusion in both 3- and 5-h muscles was significantly increased over pre- and end-ischemic values. The hydroxy-conjugated diene isomers of 18:2 and 20:4 were positively identified in reperfusion biopsies by GC-MS. These studies provide chemical evidence of free radical-mediated lipid oxidation during reperfusion of ischemic skeletal muscle.
Cardiac energetics and performance of exercised and food-restricted rats during aging
Authors: Starnes J. W. , Rumsey W. L.
Published: December 2017

The effects of exercise and food restriction on hemodynamic and metabolic characteristics of the heart during aging were studied in male, retired breeder, Fischer 344 rats. At the age of 10 mo they were divided into three groups: 1) sedentary and ad libitum fed (S); 2) sedentary and food restricted by alternate-day feeding (R); and 3) exercised 20 min/day on a treadmill and ad libitum fed (E). Isolated, perfused working hearts were analyzed at 10 (S only), 18, 24, and 30 mo. Groups E and R demonstrated significant improvements (P less than 0.01) at 18 mo for cardiac output (ml.min-1.g-1), pressure work (kg.m.min-1.g-1), and efficiency (%). These performance parameters declined (P less than 0.01) after 18 mo in all groups; however, at 24 mo, E maintained higher values (P less than 0.01) for these parameters than S or R. At 30 mo, all groups were similar. Levels of high-energy phosphate compounds or lactate release were not affected by age or treatment. An age-related increase (P less than 0.05) in left ventricular hexokinase activity was observed in all groups. Activities of rate-determining enzymes of Krebs cycle or content of cytochromes were not affected by age. We conclude from this metabolic profile that energy production is not impaired in the aged Fischer 344 rat heart.
A model of the systemic arterial bed showing ventricular-systemic arterial coupling
Authors: McIlroy M. B. , Targett R. C.
Published: December 2017

A multielement model of the systemic arterial bed was implemented on a microcomputer and was used to simulate the transient response of the arterial circulation to a specific driving function: a linearly increasing left ventricular pressure. The elements (compliances and inductances) that simulate the aorta and its branches are determined by the characteristic impedances and time delays in the arterial system. The simulations of pressure and blood velocity signals found in a previous version of the model were improved by making the delays in the system nonuniform, with slow central and rapid peripheral wave speeds. This reduced the impedance into which the heart has to pump and increased the distal impedance, raising the peripheral diastolic pressures. When the reflection coefficient was decreased as the heart rate was increased, normal pressure and velocity signals could be maintained over a range of heart rates up to 150 min-1. Extrapolating this relationship to a heart rate of 200 min-1 indicated that the reflection coefficient could be zero at that heart rate, giving optimal power transmission through the arterial bed.
Quantification of arteriolar density and embolization by microspheres in rat myocardium
Authors: Wieringa P. A. , Stassen H. G. , Laird J. D. , Spaan J. A.
Published: December 2017

We developed a technique for in vitro determination of arteriolar densities. Hearts, obtained from anesthetized rats and perfused by the Langendorff method, were fully dilated with adenosine and were arrested with an elevated potassium concentration. After a stabilization period, the hearts were perfused with a buffered fixative for some minutes to obtain a nonvital vasculature. After fixation, perfusion was switched back to control for some minutes. The hearts were then perfused with a medium containing a low concentration of microspheres: either pollen grains [Urtica dioica (15.4 microns), Betula (23.5 microns), or Phleum pratense (36.5 microns)] or polystyrene microspheres (15 microns). The perfusion was switched back to the standard medium after flow had been reduced to between 83 and 57% of control flow. Microscopic observations of microsections revealed that the percentages of arterioles embolized by one microsphere were 64% for the 15.4-microns, 74% for the 15-microns, 78% for the 23.5-microns, and 72% for the 36.5-microns microspheres. The percentages of arterioles embolized with two microspheres were 20, 15, 15, and 16%, respectively. The arteriolar densities were calculated from the total fractional reduction in coronary flow, the amount of microspheres injected, the wet heart weight, and the degree of occupancy, which corrects for the multiple embolization of the arterioles. The arteriolar densities in the rat hearts were 162.4 +/- 54.9 mg-1 (N = 6) for polystyrene microspheres of 15 microns, 161.5 +/- 81.1 mg-1 (N = 15) for 15.4-microns microspheres, 31.6 +/- 7.8 mg-1 (N = 9) for 23.5-microns microspheres, and 13.0 +/- 2.4 mg-1 (N = 8) for 36.5-microns microspheres.
Integration of heart rate and sympathetic neural effects on AV conduction
Authors: Loeb J. M. , deTarnowsky J. M.
Published: December 2017

Sympathetic activation increases heart rate (HR) and reduces atrioventricular interval (AVI), whereas atrial pacing alone increases AVI. We sought to differentiate the direct effects of sympathetic activation on atrioventricular (AV) conduction time from the indirect changes associated with concurrent alterations in HR. We recorded electrocardiograms, blood pressure (BP), and intracardiac electrograms from chloralose-anesthetized autonomically decentralized dogs. Beat-by-beat HR and AVI data were collected continuously. Sympathetic stimulation (0.25-2.5 Hz; mean 0.81 Hz) resulted in a HR change of +60 beats/min after 60 s. This tachycardia was associated with a mean decrease in AVI of 22 ms. Computer-driven atrial pacing to reproduce the HR associated with control sympathetic stimulation caused a mean AVI increase of 10 ms. Propranolol (200 micrograms) was then administered via the sinoatrial node artery and sympathetic stimulation repeated. Although HR remained constant, AVI decreased by 14.8 ms. The AVIs associated with an identical HR achieved by two different mechanisms (sympathetic stimulation and atrial pacing) were significantly different. Although removal of the contribution of sympathetically induced HR changes on AV conduction might be expected to result in potentiation of neural effects at the AV node, none was evident. Thus sympathetic activity restricted to the AV node is less effective in influencing AV conduction than the response that occurs when HR changes occur concurrently. Therefore, the opposing actions of HR and sympathetic tone on AV conduction may not be predicted by a simple linear relationship.
Depressor neurons in rabbit caudal medulla act via GABA receptors in rostral medulla
Authors: Blessing W. W.
Published: December 2017

Experiments were conducted in urethan-anesthetized rabbits to determine whether vasomotor effects elicited by activation or inhibition of the caudal ventrolateral medulla depend on gamma-aminobutyric acid (GABA)ergic, glycinergic, or alpha-adrenergic receptors in the region of the rostral ventrolateral medulla, which contains the bulbospinal sympathoexcitatory neurons. Bilateral injection of bicuculline methiodide into the rostral medulla caused a dose-related reduction in the fall in arterial pressure and in the inhibition of renal sympathetic nerve activity normally elicited by chemical stimulation of neurons in the caudal medulla using local injection of L-glutamate. When both bicuculline and muscimol were injected into the rostral medulla at the same time, resting arterial pressure was maintained at base-line levels, and the sympathoexcitatory neurons remained normally excitable by local injection of L-glutamate into the rostral medulla. In the presence of this mixed antagonist-agonist GABAergic blockade, both decreases and increases in arterial pressure elicited by excitation or inhibition of neuronal function in the caudal medulla were abolished. Similar effects were not observed after blockade of glycinergic or alpha-adrenergic receptors in the rostral ventrolateral medulla. Results suggest that the depressor neurons in the caudal ventrolateral medulla alter peripheral sympathetic vasomotor activity almost entirely by an action on GABAergic receptors in the rostral ventrolateral medulla.
Central blood volume and blood pressure in conscious primates
Authors: Cornish K. G. , Gilmore J. P. , McCulloch T.
Published: December 2017

Conscious intact (I) and sinoaortic-denervated monkeys (SAD) were studied to determine the extent to which high-pressure receptors contribute to the maintenance of arterial blood pressure (BP) when venous return is decreased by hemorrhage (H) or lower body negative pressure (LBNP). In the I animals, mean BP did not decrease significantly until 5% of the estimated blood volume (EBV) was removed, whereas, with sinoaortic denervation, mean BP decreased significantly when less than 2% of EBV was removed. Left atrial pressure (LAP) decreased similarly in both groups of animals. In the I group during LBNP, mean BP did not change significantly, whereas pulse pressure decreased significantly when LBNP was decreased to -5 cmH2O. In the SAD animals, mean BP decreased significantly at an LBNP of -2 cmH2O, and at -5 cmH2O mean BP declined from 134.1 +/- 4 to 102.7 +/- 7 mmHg. LAP decreased similarly in both groups of animals. The data support the view that a nonhypotensive reduction in venous return unloads arterial baroreceptors sufficiently to activate the arterial baroreflex, probably through reductions in pulse pressure. In addition, low-pressure receptors by themselves do not appear to contribute importantly to blood pressure maintenance when venous return is decreased by either LBNP or a nonhypotensive hemorrhage.
Effect of fluorocarbon-for-blood exchange on regional cerebral blood flow in rats
Authors: Lee P. A. , Sylvia A. L. , Piantadosi C. A.
Published: December 2017

Cerebrocirculatory responses to total perfluorocarbon (FC-43)-for-blood replacement (Hct less than 1%) were studied in anesthetized, ventilated rats breathing 100% O2. Changes in total and regional cerebral blood flow (CBF) were measured using the radiolabeled-microsphere technique. The data were compared with two control groups of hemoglobin-circulated animals; one group was exposed to arterial hypoxia (arterial PO2 = 40 Torr) and the other to isovolemic hemodilution with Krebs-Henseleit-albumin (KHA) solution (mean Hct = 11%). Exchange transfusion with FC-43 doubled total and regional CBF, causing preferential flow increases to the cortex and cerebellum. Estimated cerebrovascular resistance fell to 50% of the preexchange value. Both hemodilution and hypoxia control experiments produced CBF responses similar to those obtained in FC-43 animals. Although calculated arterial O2 contents in all three groups of animals were similar, blood viscosity was normal in hypoxic rats and reduced in KHA and FC-43 animals. Since arterial and cerebrovenous PO2s were both high in fluorocarbon-circulated rats, our results suggest that decreased O2 content and perhaps lower viscosity of the circulating fluorocarbon were responsible for increases in CBF required to maintain sufficient delivery of O2 to the brain.
Electrophysiological evidence for alpha 1- and alpha 2-adrenoceptors in solitary tract nucleus
Authors: Feldman P. D. , Moises H. C.
Published: December 2017

The effects of microiontophoresis of norepinephrine and epinephrine were examined on the spontaneous neuronal activity of single neurons in the nucleus tractus solitarius (NTS) in urethan-anesthetized rats. Neuronal responses to catecholamine iontophoresis were examined in the absence and presence of the alpha 1-adrenergic antagonist, prazosin, and the alpha 2-antagonist, idazoxan, to characterize the subtypes of alpha-adrenergic receptors mediating catecholamine action in this important autonomic nucleus. Norepinephrine produced inhibitions in firing, which were blocked primarily by idazoxan, whereas epinephrine-induced neuronal inhibitions were blocked by either prazosin or idazoxan. Inhibitions of spontaneous firing were also produced by iontophoresis of methoxamine, an alpha 1-selective agonist, or the alpha 2-selective agonist clonidine in all neurons that were tested. Neuronal responses to methoxamine were blocked selectively by prazosin, whereas the effects of clonidine were antagonized selectively by idazoxan. These data provide evidence at the level of the single unit that catecholamines may affect activity in the NTS via interactions with both alpha 1- and alpha 2-adrenergic receptors.
Role of platelets in maintenance of pulmonary vascular permeability to protein
Authors: Lo S. K. , Burhop K. E. , Kaplan J. E. , Malik A. B.
Published: December 2017

We examined the role of platelets in maintenance of pulmonary vascular integrity by inducing thrombocytopenia in sheep using antiplatelet serum (APS). A causal relationship between thrombocytopenia and increase in pulmonary vascular permeability was established by platelet repletion using platelet-rich plasma (PRP). Sheep were chronically instrumented and lung lymph fistulas prepared to monitor pulmonary lymph flow (Qlym). A balloon catheter was positioned in the left atrium to assess pulmonary vascular permeability to protein after raising the left atrial pressure (Pla). Thrombocytopenia was maintained for 3 days by daily intramuscular APS injections. Platelet count decreased from 460,000 +/- 77,000 to 16,000 +/- 4,000 platelets/microliters, without significant changes in the leukocyte count and hematocrit. Studies were made in three groups: 1) control sheep having a normal platelet count; 2) thrombocytopenic sheep; and 3) PRP-infused thrombocytopenic sheep. Elevation in Pla in control sheep increased pulmonary transvascular protein clearance (CL) to 12.1 +/- 2.1 ml/h, whereas the same Pla elevation in thrombocytopenia increased CL to 24.1 +/- 4.0 ml/h, indicating an increase in pulmonary vascular permeability to protein in thrombocytopenic animals. Infusion of PRP restored normal permeability, since it prevented the increase in CL. In studies using cultured bovine pulmonary artery endothelial monolayers, transendothelial permeability of 125I-labeled albumin was reduced 50 and 95%, respectively, when 2.5 X 10(7) or 5 X 10(7) platelets were added onto endothelial monolayers. However, addition of 5 X 10(6) platelets or 5 X 10(7) red blood cells did not reduce endothelial monolayer albumin permeability.(ABSTRACT TRUNCATED AT 250 WORDS)
On-line measurement of aortic valve ring deformation during the cardiac cycle
Authors: van Renterghem R. J. , Arts T. , van Steenhoven A. A. , Reneman R. S.
Published: December 2017

An electronic device is described for the measurement of relative changes in segment length within the aortic valve ring during the cardiac cycle. The technique is based on the principle of magnetic induction. A magnetic field generated in one coil induces a voltage in another coil. From the amplitude of this voltage the strain between both coils can be determined because the strength of the magnetic field decreases with distance. In vitro, over a range of 5-25 mm, strains less than or equal to 0.20 strain units can be measured with an accuracy of 0.008 strain units. The frequency response is 0-150 Hz (-3 dB). By varying the generator and receiver assignment at a frequency of 2 kHz and multiplexing the signals of six coils, six strains can be measured simultaneously. As an example, simultaneous recordings of commissure strains in the aortic valve and left ventricular and ascending aortic pressures, as obtained in open-chest dogs, are shown.
A simple method for measurement of left ventricular septal-lateral dimension
Authors: Freeman G. L. , Watkins D. , Little W. C.
Published: December 2017

In studies of myocardial performance of the intact heart, continuous measurement of the left ventricular septal-lateral diameter provides useful information. We describe a technique for placing a piezoelectric diameter gauge on the left ventricular endocardium of the intraventricular septum. This technique is simple and relatively atraumatic. It provides a way to evaluate septal-lateral dimension in either acute or chronic experiments and produces a stable signal that represents the instantaneous septal-lateral dimension of the left ventricle.