bluuebunny/crossref_metadata_2025 huggingface dataset:
Postnatal carbon monoxide exposure: immediate and lasting effects in the rat
Authors: Penney D. G. , Baylerian M. S. , Thill J. E. , Fanning C. M. , Yedavally S.
Published: December 2017

Groups of newborn rats inhaled 500 ppm CO for 32 days, after which they continued development in ambient air. The ratio of heart weight to body weight increased sharply after birth, peaked at 14 days of age, and then fell progressively but remained above that of normal rats at 68 and 107 days of age. At 14 days of age, the weight of the left ventricle plus interventricular septum (LV + S) exceeded the controls by 80%, whereas the weight of the right ventricle (RV) was 100% greater. RV weight remained significantly greater than that of the controls at 68, 107, and 217 days of age. The ratio of RV weight to LV + S weight remained higher than that of the controls both during and after CO exposure. Myocardial deoxyribonucleic acid (DNA) concentration (microgram/mg dry wt) declined more rapidly in the CO-exposed groups during the first 2 wk. DNA content (microgram/LV + S + RV) was not significantly different. There were no differences in DNA concentration or content after CO exposure. Hydroxyproline, used as an index of collagen content, was unaffected by postnatal cardiomegaly. Hydroxyproline concentration was depressed only during the first 3 wk. Cardiac cytochrome c concentration was depressed and lactate dehydrogenase M subunit composition elevated only during CO exposure. Neither lactate dehydrogenase specific activity nor myoglobin concentration was altered during or after CO treatment. Neither the DNA nor hydroxyproline data provide an explanation for "persistent cardiomegaly."
Accumulation of [3H]norepinephrine in canine saphenous vein: influence of plasma
Authors: Freas W. , Muldoon S. M. , Haddy F. J.
Published: December 2017

This study was designed to systematically characterize the neuronal and extraneuronal uptake systems for norepinephrine (NE) in isolated nerve-rich vascular tissue and then to explore the possibility that circulating factors may alter these uptake systems. Strips from canine saphenous vein were incubated in Krebs-Ringer solution containing L-[3H]NE, and both tissue and medium were analyzed for total tritium, [3H]NE, and [3H]metabolite content. Under these conditions neuronal uptake (uptake1) played the dominant role in NE disposition. The addition of cocaine, ouabain, or potassium or the reduction of sodium decreased the activity of uptake1, and extraneuronal uptake (uptake 2) then played a major role in NE metabolism. The addition of 30, 60, and 90% plasma reduced NE accumulation and 3,4-dihydroxyphenylglycol (DOPEG) formation to 71 and 62% of control values, respectively; the formation of normetanephrine (NMN) and O-methylated deaminated compounds (OMDA) was not significantly different. In the presence of cocaine and uptake 1 inhibitor, 30% plasma did not cause a further significant decrease in neuronal accumulation of NE. The inhibitory activity of plasma on NE accumulation was not significantly affected by boiling or standing at room temperature for 45 min. These studies show that in the isolated canine saphenous vein the addition of plasma, like low sodium, cocaine, or ouabain, decreases neuronal uptake. The identity of the component in plasma responsible for inhibition of NE uptake appears to be a nonprotein, heat-stable molecule.
Acetylcholine inhibits positive inotropic effect of cholera toxin in ventricular muscle
Authors: Pappano A. J. , Hartigan P. M. , Coutu M. D.
Published: December 2017

Acetylcholine (ACh, 10(-6) M) had no effect on basal adenylate cyclase activity (3.4 +/- 0.56 pmol cyclic AMP . min-1 . mg wet wt-1), adenosine 3',5'-cyclic monophosphate (cyclic AMP) content (0.88 +/- 0.09 pmol/mg wet wt), or the force of contraction in paced (2.5 Hz) chick embryo right ventricles superfused with Tyrode solution. After 60-180 min of superfusion in the presence of cholera toxin (5 x 10(-6) g/ml), adenylate cyclase activity (1.7 times), cyclic AMP content (2.4 times), and contractility (2.4 times) had increased significantly above basal levels. ACh reversed the positive inotropic effect of cholera toxin but did not change the increased activity of adenylate cyclase and content of cyclic AMP obtained in cholera toxin. Stimulation of adenylate cyclase by isoproterenol (ISO) was inhibited by ACh in the absence and presence of cholera toxin. ACh did not change guanosine 3',5'-cyclic monophosphate (cyclic GMP) content in the absence or presence of cholera toxin. Cholera toxin has actions on chick embryo ventricle similar to those of the beta-adrenergic agonist, ISO, and the phosphodiesterase inhibitor, isobutylmethylxanthine. The ability of ACh to reverse the positive inotropic effect of cholera toxin without preventing the accumulation of cyclic AMP may involve the prevention or reversal of cyclic AMP-dependent phosphorylation. In this regard, reduction of Ca2+ influx through voltage-sensitive membrane channels may be an essential component of muscarinic inhibition.
Effect of aminophylline on coronary functional hyperemia and myocardial adenosine
Authors: Jones C. E. , Hurst T. W. , Randall J. R.
Published: December 2017

The role of adenosine in coronary functional hyperemia was tested using the adenosine antagonist aminophylline. In 11 dogs left coronary blood flow (LCBF) and left ventricular oxygen extraction [(a-v)O2] were monitored. Myocardial oxygen consumption (MVO2) was calculated. Before aminophylline was administered, intracoronary infusion of 6.8 micrograms/min norepinephrine increased LCBF and MVO2 by 40-80%. Simultaneous infusion of adenosine further increased LCBF. Fifteen minutes after injection of 100 mg aminophylline, norepinephrine still increased LCBF, and the ratio delta LCBF/delta MVO2 was unchanged (P greater than 0.05). Although the functional hyperemia was not blunted, the response to infused adenosine was abolished by aminophylline. In 20 additional dogs myocardial adenosine was determined. Before norepinephrine infusion myocardial adenosine with and without aminophylline was 12.7 and 14.3 nmol/g dry wt, respectively (P greater than 0.05). During norepinephrine infusion an increase in adenosine correlated well with increases in MVO2 and LCBF, but the increase in adenosine was not greater after aminophylline. Thus the failure of aminophylline to blunt functional hyperemia was not due to a higher adenosine level after aminophylline. These results do not support a role for adenosine in functional hyperemia elicited by norepinephrine.
alpha-Naphthylthiourea produces dose-dependent lung vascular injury in sheep
Authors: Havill A. M. , Gee M. H. , Washburne J. D. , Premkumar A. , Ottaviano R. , Flynn J. T. , Spath J. A.
Published: December 2017

We tested the effects of alpha-naphthylthiourea (ANTU) on lung fluid balance and prostanoid concentrations in anesthetized sheep acutely prepared for collection of pulmonary lymph. Sheep were given 20, 50, 75, or 100 mg/kg ANTU or the vehicle dimethylsulfoxide (DMSO) intravenously. The first phase of the response consisted of transient increases in pulmonary artery pressure and plasma and lymph thromboxane B2 concentrations. Lymph flow increased with no change in the lymph-to-plasma protein concentration ratio (L/P). These changes occurred in sheep given DMSO alone or DMSO with ANTU; they were not dependent on the dose of ANTU given. Two to 4 h after drug administration, pulmonary artery pressure and thromboxane concentrations were normal or near normal. Lymph flow rate reached steady-state levels averaging 1.5 (DMSO alone) to 5.3 (100 mg/kg ANTU) times base line with L/P ratios unchanged from base line. ANTU/DMSO produces transient, severe pulmonary hypertension that may be prostaglandin mediated. The sustained response consists of increased flow rate of protein-rich lymph.
Systemic and regional hemodynamic effects of endogenous vasopressin stimulation in rats
Authors: Charocopos F. , Hatzinikolaou P. , North W. G. , Gavras H.
Published: December 2017

We investigated the systemic and regional hemodynamic alterations induced in normotensive anephric rats by stimulation of endogenous vasopressin with an acute sodium and fluid load and following vasopressin inhibition with a specific antagonist of its vasoconstricting action. Blood pressure and total peripheral resistance were significantly higher and cardiac output was lower in rats with stimulated vasopressin, and all were reversed to near control levels in rats receiving the vasopressin inhibitor. Regional blood flows were diminished in most organs and local vascular resistance was elevated compared with control animals, but the magnitude of change varied widely. In fact, heart blood flow did not decrease significantly and brain blood flow actually increased indicating small or no change in vascular resistance of these organs. Moreover, fractional distribution of the diminished cardiac output to these organs was significantly higher, so that blood flow to vital organs was maintained at the expense of blood flow to other tissues. In rats that received the vasopressin antagonist after the saline infusion, regional blood flows were similar to those of control animals. Blood pressures at the base line and after hypertonic NaCl infusion correlated closely with the corresponding plasma levels of control and stimulated vasopressin.
Effect of an anteroventral third ventricle lesion on NaCl hypertension in Dahl salt-sensitive rats
Authors: Goto A. , Ganguli M. , Tobian L. , Johnson M. A. , Iwai J.
Published: December 2017

An anteroventral third ventricle (AV3V) lesion in the brain prevents several forms of experimental hypertension. The present experiment was designed to determine whether the AV3V lesion prevents NaCl-induced hypertension in Dahl salt-sensitive (S) rats and whether attenuation of vasopressin release reported in lesioned rats contributes to the protective effect of the AV3V lesion against hypertension. After the AV3V lesion Dahl S rats received daily injections of either vasopressin (pitressin tannate, 500 mU/kg) or vehicle during 10 wk of 8% high-NaCl diet. Sham-lesioned rats served as controls. The blood pressure in sham-lesioned rats receiving vehicle was 189 mmHg after 10 wk of high-NaCl diet. Lesioned rats given vehicle showed a significantly smaller increase in blood pressure than sham-lesioned rats (P less than 0.001), the blood pressure averaging 161 mmHg at 10 wk. Lesioned rats given vasopressin also showed a smaller increase in blood pressure than sham-lesioned rats (P less than 0.05), but the final blood pressure averaged 176 mmHg and was significantly higher than that of lesioned rats given vehicle (P less than 0.025). Vasopressin injections corrected the hypernatremia in lesioned rats. In another experiment the effect of the AV3V lesion on the renal papillary plasma flow (RPPF) in Dahl S rats was studied. Dahl S rats have a lower RPPF than Dahl salt-resistant (R) rats even on a low-NaCl intake. The AV3V lesion increased the RPPF by 14% in S rats (P less than 0.025). These findings suggest that NaCl-induced hypertension in Dahl S rats requires the integrity of the AV3V region for its full expression, and the ability of the AV3V lesion to attenuate the NaCl-induced hypertension in Dahl S rats is partly related to the attenuation of vasopressin release. Moreover, the AV3V lesion partly corrected one of the characteristic features of Dahl S rats, the reduction in RPPF, when compared with Dahl R rats, with both strains on a low-NaCl intake.
Factors modifying contraction-relaxation cycle in vascular smooth muscles
Authors: Kuriyama H. , Ito Y. , Suzuki H. , Kitamura K. , Itoh T.
Published: December 2017

Contraction-relaxation cycles in vascular smooth muscles are largely dependent on the regulation of free Ca2+ in the myoplasm, as is the case in skeletal and cardiac muscles. In this article we describe the varieties of contraction-relaxation cycles of vascular smooth muscles determined at cellular and subcellular levels. To discuss the excitation-contraction and pharmacomechanical coupling mechanisms in vascular tissues, passive and active membrane properties and ionic movements measured by various procedures are briefly introduced. In vascular smooth muscles the sources of Ca2+ contributing to the activation of contractile proteins are extra- and intracellular. Influxes of Ca2+ across the membrane are enhanced by the calcium spike and electrical and chemical depolarizations or activations of autonomic receptors.l However, the Ca2+ influx during the generation of action potential does not directly increase the free Ca2+ in the cell; rather, this ion is sequestered in the storage site and activates the calcium-induced calcium-release mechanism in the storage sites with a subsequent increase in the levels of free Ca2+. In some vascular tissues depolarizations induced by activations of autonomic receptors are not a prerequisite for generation of the contraction, as these mechanical responses appear with hyperpolarization of the membrane or without a change in the membrane potential. Possible functional links between the myoplasmic membrane where the receptors are distributed and the Ca2+ storage and releasing sites (mainly sarcoplasmic reticulum) in the cell are discussed. In addition, small arteries possess possibly more than three subtypes of alpha-adrenoceptors, including the presynaptic alpha 2-adrenoceptor. The roles of sarcoplasmic reticulum and the calcium receptor of contractile proteins (calmodulin or leiotonin C) from the chemically skinned muscles of vascular tissues were compared with those of intact muscles. The relaxation of vascular tissues as induced by activations of beta-adrenoceptors, nitrites, and other chemicals is also briefly introduced.
Cardiac output distribution during vasopressin infusion or dehydration in conscious dogs
Authors: Liard J. F. , Deriaz O. , Schelling P. , Thibonnier M.
Published: December 2017

To better understand the role of arginine vasopressin in cardiovascular regulation, we measured in unanesthetized dogs regional blood flows with radioactive microspheres before and during 1-h vasopressin infusions that increased the vasopressin concentration of plasma by 11 +/- 0.6 pg/ml. Cardiac output measured by an electromagnetic flowmeter decreased by 13%. Blood flows to the skeletal muscle and skin, the areas most affected, decreased by 30.8 and 34.3%, respectively. In the same group of dogs a period of 48-h water restriction increased plasma vasopressin by 6.9 +/- 1.3 pg/ml and reduced cardiac output by 14.4%. Skeletal muscle blood flow decreased by 32.8%, a pattern strikingly similar to that following vasopressin infusion. Obvious differences between vasopressin infusion and dehydration were also noted, in particular in the skin and splanchnic areas. However, the possibility that vasopressin contributed to the cardiovascular adjustments to dehydration must be considered. The use of an antagonist of the vascular effects of vasopressin, [1-deaminopenicillamine, 2-(O-methyl)tyrosine]arginine-vasopressin ([dPTyr(Me)]AVP), did not permit us to clarify this issue, because this analogue given alone exerted pronounced systemic and regional cardiovascular effects that resembled those of vasopressin.
Mechanisms of initial heart rate response to postural change
Authors: Borst C. , Wieling W. , van Brederode J. F. , Hond A. , de Rijk L. G. , Dunning A. J.
Published: December 2017

We explored in 43 healthy subjects the afferent mechanisms of the initial heart rate response to standing by comparing free standing, 70 degrees head-up tilt, handgrip, and contraction of abdominal and leg muscles. The results indicate the following. 1) Standing evokes an immediate, large, bimodal increase of heart rate (HR) of about 20 s duration that far exceeds the gradual HR rise induced by 70 degrees head-up tilt. 2) The immediate HR increase with active standing is due to the exercise reflex and results in a first peak about 3 s after standing briskly. 3) The secondary, more gradual HR increase after 5 s of standing and the subsequent rapid decrease of HR between about 12 and 20 s corresponds through the baroreceptor reflex with a striking fall, recovery, and sometimes overshoot of arterial pressure. 4) The maximum HR increase found after about 12 s of standing is augmented and delayed after rest. 5) The time course of the initial HR response is not modified by physical training. We conclude that active and passive changes of posture result in fundamentally different cardiovascular effects for about 20 s and that "central command," muscle receptors, high-pressure receptors, low-pressure receptors, and the plasma catecholamine level are probably all involved in the initial HR response to standing.
Effect of thyroxine treatment on exogenous myocardial lactate oxidation
Authors: Fintel M. , Burns A. H.
Published: December 2017

The effect of thyroxine treatment on myocardial lactate oxidation was examined by use of an isolated, working rat heart preparation. Thyroxine treatment, both acute and chronic, was associated with a decrease in lactate oxidation, when the heart was perfused with a physiological blend of substrates (free fatty acids, lactate, and glucose). This decrease in lactate oxidation was not caused by a generalized impairment in mitochondrial oxidation of acetyl coenzyme A (CoA), as oxygen consumption was normal and fatty acid oxidation was elevated in the treated animals. The block in lactate oxidation was localized to the conversion of pyruvate to acetyl CoA, as indicated by the depressed oxidation of pyruvate and lactate. Thyroxine treatment was associated with a decrease in pyruvate dehydrogenase activity. The decrease in pyruvate dehydrogenase activity was reversible and was attributed to the enhanced myocardial oxidation of free fatty acids.
Sympathoadrenal mechanisms in hemodynamic responses to gastric distension in cats
Authors: Longhurst J. C. , Ibarra J.
Published: December 2017

There is presently little information on the efferent mechanisms responsible for the reflex cardiovascular activation during passive gastric distension. Therefore, 40 cats anesthetized with alpha-chloralose were studied with passive gastric balloon distention before and during 1) two repeated gastric distensions, 2) beta-adrenergic blockade with propranolol, 3) alpha-adrenergic blockade with phentolamine, or 4) bilateral adrenalectomy. Before and during each distension mean arterial pressure, heart rate, cardiac output, rate of rise of left ventricular pressure (dP/dt) at 40 mmHg developed pressure and calculated systemic vascular resistance were determined. Repeated gastric distension caused similar hemodynamic responses without tachyphylaxis. beta-Blockade significantly reduced the increase in dP/dt from 893 +/- 362 to 150 +/- 63 mmHg/s. alpha-Blockade significantly altered the changes in mean arterial pressure from 33 +/- 5.0 to -2 +/- 4.7 mmHg and systemic vascular resistance from 0.114 +/- 0.019 to 0.004 +/- 0.031 peripheral resistance units. Bilateral adrenalectomy significantly diminished the contractile response from 525 +/- 107 to 50 +/- 85 mmHg/s but did not significantly alter the pressor and vasoconstrictor responses. We conclude that, during passive gastric distension in cats, the increase in myocardial contractility is mediated by beta-adrenergic-receptor stimulation, whereas the arterial vasoconstrictor and pressor responses are mediated by alpha-adrenergic receptor stimulation. Additionally, during gastric distension a substantial portion of the contractile response is dependent on the integrity of the adrenal glands.
A programmable pressure control system for coronary flow studies
Authors: Canty J. M. , Mates R. E.
Published: December 2017

An electrohydraulic servo valve capable of reproducing phasic physiological pressure and flow waveforms has been designed and constructed. The device has been utilized successfully in canine coronary flow studies. By measuring coronary pressure directly it is possible to reproduce waveform frequency components as high as 50 Hz in the cannulated left circumflex coronary artery when operated in a negative feedback configuration. It may easily be adapted to operate in a pressure- or flow-controlled mode in any vascular bed. The closed-loop frequency response of the servo valve itself is flat to 100 Hz with a natural frequency of 170 Hz. When utilized in the cannulated bed the frequency response is dependent on perfusion circuit and catheter dynamics.
Baroreflex regulation of renal nerve activity during volume expansion
Authors: Thames M. D. , Miller B. D. , Abboud F. M.
Published: December 2017

Volume expansion could inhibit renal nerve activity by stimulating cardiopulmonary baroreflexes or by increasing arterial pressure (i.e., stimulating the sinoaortic baroreflexes). Our study assessed the relative roles of these two reflexes in the renal nerve activity responses to volume expansion (15 ml/kg 6% dextran in normal saline). With cardiopulmonary and arterial baroreflexes intact, volume expansion resulted in increases in arterial pressure and pulmonary artery wedge pressure and in decreases in renal nerve activity. After sinoaortic denervation, volume expansion resulted in similar decreases in renal nerve activity for similar increases in pulmonary artery wedge pressure. In contrast, after selective vagotomy (sinoaortic baroreflexes intact) volume expansion resulted in increases in arterial pressure and pulmonary artery wedge pressure, but reductions in renal nerve activity were markedly attenuated. After sinoaortic denervation and vagotomy, volume expansion did not result in significant changes in renal nerve activity. We conclude that decreases in renal nerve activity during volume expansion are mediated mainly by cardiopulmonary receptors with afferent vagal fibers. Sinoaortic baroreceptors appear to play a minor role in mediating these responses.
Skeletal muscle and cardiac changes with training in patients with angina pectoris
Authors: Ferguson R. J. , Taylor A. W. , Cote P. , Charlebois J. , Dinelle Y. , Peronnet F. , De Champlain J. , Bourassa M. G.
Published: December 2017

Cardiovascular and skeletal muscle adaptations were studied before and after 6 mo of physical training in patients with coronary artery disease and exertional angina pectoris. Symptom-limited exercise capacity increased by 41% (470 +/- 30 to 665 +/- 35 kg.m.min-1; n = 29, P less than 0.001) with training as did skeletal muscle succinate dehydrogenase activity (1.75 +/- 0.24 to 3.31 +/- 0.24 IU; n = 23, P less than 0.001) and the areas of muscle fibers (type I from 43.6 +/- 3.3 to 54.4 +/- 3.3 micrometers 2 X 10(2); n = 21, P less than 0.05 and type II from 43.9 +/- 2.4 to 57.2 +/- 5.1 micrometers 2 X 10(2); P less than 0.01). At the same submaximal exercise intensity (mean 355 +/- 100 km.m.min-1), plasma catecholamines (1.31 +/- 0.14 to 1.07 +/- 0.09 ng.ml-1; n = 13, P less than 0.05), heart rate (115 +/- 3 to 97 +/- 3 beats/min; n = 29, P less than 0.001), and systolic blood pressure (171 +/- 4 to 143 +2- 4 mmHg; n = 29, P less than 0.001) were significantly reduced after training. Maximal coronary sinus blood flow (192 +/- 10 to 208 +/- 9 ml.min-1; n = 29, P less than 0.05) and left ventricular oxygen consumption (23.2 +/- 1.5 to 25.8 +/- 1.6 ml.min-1; n = 24, P less than 0.05) were increased by 8 and 11%, respectively, after training. The improvement in exercise capacity with training in patients with exercise is secondary to a reduction in myocardial oxygen requirements during subangina levels of exercise and partly to a small increase in maximal myocardial oxygen consumption. The skeletal muscle adaptations with training were not related to other indices of training such as the reduced exercise heart rate or increased symptom-limited exercise capacity.
Hindlimb resistance in hypoxic dogs after adrenergic blockade or denervation
Authors: Cain S. M. , Chapler C. K.
Published: December 2017

Blood flow (Q) and O2 uptake (Vo2) were measured in the intact autoperfused left hindlimb (less paw) of anesthetized paralyzed dogs ventilated at constant rate with either room air (normoxia) or 9.1% O2 in N2 (hypoxia) for 20-min periods. One group of 10 dogs was given 3.0 mg/kg phenoxybenzamine (alpha-block) and was subjected to the sequence of normoxia, hypoxia, normoxia. The sequence was repeated after 1.0 mg/kg propranolol (beta-block). A second group of 10 was treated the same but was not given adrenergic blockers (no block). A third group of 10 was made hypoxic only once after the sciatic and femoral nerves to the prepared limb were severed (denervated). Decreased O2 availability during hypoxia limited both total and limb V02 in all cases. Limb Q did not change, but vascular resistance increased in the no-block group with onset of hypoxia and a brisk transient hyperemia occurred with reoxygenation. After both alpha- and beta-block no change occurred in limb resistance with reoxygenation. A similar result was obtained in the denervated limb. These results indicated that the transient hyperemia following hypoxia was the result of altered states of neurally mediated vascular tone, mostly sympathetic, and was not due to local metabolic vasodilation or altered blood levels of catecholamines during a 20-min period of hypoxia.
Anesthetic depression of microcirculation, central hemodynamics, and respiration in decerebrate rats
Authors: Faber J. E. , Harris P. D. , Wiegman D. L.
Published: December 2017

The objectives of this study were the development of a skeletal muscle microcirculatory preparation, in which the complications of drug anesthesia were minimized, and the quantitation of the effects of urethan and chloralose anesthesia on the microcirculation. Rats were initially anesthetized with urethan and chloralose and decerebrated by a midcollicular transection. The cremaster skeletal muscle, with intact circulation and innervation, was prepared for intravital microscopy by placement in a tissue bath. Arterioles (9–70 micrometers diam) at several anatomic levels were observed during the initial period of urethan-chloralose anesthesia (period 1), after recovery from the anesthesia (period 2), and again following reanesthetization (period 3). During period 2, respiratory rate, heart rate, and mean arterial pressure were significantly greater than during periods 1 and 3. Smaller arterioles (8–50 micrometers diam) exhibited vasomotion (mean amplitude 35% of mean diameter; mean frequency 31 cycles/min) during period 2. Urethan-chloralose anesthesia during periods 1 and 3 inhibited vasomotion and increased arteriolar diameters by 16–36%. This study quantitates the depressant effects of urethan-chloralose anesthesia on the cardiovascular system and demonstrates the feasibility of using decerebration to circumvent the necessity of continuous drug anesthesia for in vivo microvascular studies.
Contrasting ischemic contraction patterns by zone and layer in canine myocardium
Authors: Hattori S. , Weintraub W. S. , Agarwal J. B. , Bodenheimer M. M. , Banka V. S. , Helfant R. H.
Published: December 2017

The effect of graded coronary occlusion on myocardial shortening in different zones of the left ventricle is not clear. Therefore, in 15 dogs ultrasonic crystals were used to evaluate the effect of graded coronary occlusion on subendocardial and subepicardial contraction in both the left anterior descending coronary artery (LAD) and left circumflex coronary artery (Circ) distributions. Subepicardial shortening was evaluated along both the long and short axes. In the LAD zones, segment shortening decreased in parallel in the subendocardium and subepicardium. In the circumflex zone subendocardial and subepicardial long axis shortening fell off in parallel, while subepicardial short axis shortening fell off more rapidly. Thus there is a close relationship between endocardial and epicardial segment shortening following graded coronary occlusion. In the circumflex zone, however, fiber orientation may affect the measurement of segment motion.
Ouabain binding and potassium relaxation in aortas from renal hypertensive rabbits
Authors: Hagen E. C. , Johnson J. C. , Webb R. C.
Published: December 2017

This study was designed to characterize the electrogenic sodium pump in vascular smooth muscle from one-kidney one-clip (1K-1C), renal hypertensive rabbits. Two measures of the electrogenic pump were used: 1) [3H]ouabain binding and 2) potassium-induced relaxation. The binding study indicated a significant increase in the affinity of pump sites for ouabain in aortic strips from hypertensive rabbits compared with those from normotensive rabbits (Scatchard analysis). The maximal binding capacity of the binding sites was similar in the two groups of animals, whereas the concentration of ouabain at which half-maximal binding occurred was lower in the aortic strips from hypertensive rabbits. Aortic strips from hypertensive rabbits showed greater sensitivity to the relaxant effect of potassium after incubation in potassium-free solution. The potassium-induced relaxation in aortic strips from hypertensive rabbits was more sensitive to the inhibitory effect of ouabain than that in strips from normotensive rabbits. These results suggest that the increased sensitivity to potassium and ouabain in vascular smooth muscle from hypertensive rabbits is due to an increased affinity of the pump sites for these substances.
Use of tibial length to quantify cardiac hypertrophy: application in the aging rat
Authors: Yin F. C. , Spurgeon H. A. , Rakusan K. , Weisfeldt M. L. , Lakatta E. G.
Published: December 2017

Fluctuations in body weight as occur with aging make body weight an unreliable reference for normalizing heart weight. We compared heart weight normalized by tibial length, which remains constant after maturity, with that normalized by body weight in 5- to 28-mo-old male Wistar rats. When normalized by tibial length or body weight, relative to the 5-mo heart, the senescent left ventricle undergoes 17 vs. 38% hypertrophy, respectively, and the right ventricle undergoes 0 vs. 28% hypertrophy, respectively. Histological measurements in the 25- compared with the 5-mo-old left ventricles reveal 6% larger myocyte diameters and 12% larger cellular cross-sectional areas, indicating about 15% hypertrophy; this value agrees more closely with the estimates based on tibial length than with those based on body weight. To allow prediction of left ventricular weight in a living rat, a regression equation using body weight, age, and tibial length was derived. This enabled us to perform a longitudinal aging study that verified that the above results were not biased by selective survival. Thus, in conditions in which body weight changes, cardiac hypertrophy can be more accurately quantified by relating heart weight to tibial length than to body weight. This approach may have applicability for assessing relative sizes of other organs as well.
Effect of exercise in healthy men on QRS power spectrum
Authors: Bhargava V. , Goldberger A. L.
Published: December 2017

The effect of exercise on the QRS power spectrum has not been evaluated. We hypothesized that increased conduction velocity with exercise might selectively increase high-frequency QRS potentials. Using a digital electrocardiograph (ECG) cart, a single bipolar chest lead was recorded in 21 healthy adult males at rest and then immediately after treadmill exercise. Fast Fourier transform analysis of the ECGs was performed using a 128-ms sampling window, including the QRS but not the P wave. Step discontinuities between PR and ST segments were minimized using a linear correction function to obviate artifactual increases in high-frequency content after exercise. The power spectrum plots of rest and exercise data showed an increase in the amplitude of high frequencies that could not be accounted for on the basis of noise contamination. For the frequency band between 187.5 and 250 Hz, the root-mean-square (RSM) voltage of exercise QRS complexes (10.0 +/- 3.6 micro V) was significantly (P less than 0.02) greater than that of rest QRS complexes (7.8 +/- 1.2). However, base-line noise level (computed over a 32-ms interval during the ST segment) was not different between rest and exercise over this high-frequency band. The same exercise protocol was also applied in 11 normal male subjects using an analog ECG cart. For the 187.5- to 250-Hz band, the RMS voltage of the QRS after exercise (13.0 +/- 1.8 micro V) was also significantly (P less than 0.01) greater than at rest (10.2 +/- 2.8) without any difference in ST segment noise level over the same frequency range. These data indicate that exercise causes an increase in the amplitude of high-frequency QRS potentials in healthy men.
Peripheral vascular effects of nitroglycerin in a conscious rat model of heart failure
Authors: Flaim S. F.
Published: December 2017

The effects of intravenous nitroglycerin (NG; 2, 8, 32 micrograms/kg) on cardiocirculatory dynamics were evaluated in control normal (C) and chronically volume-overloaded [high-output heart failure (aortocaval fistula), HCO] conscious rats. Pressures were recorded in the left ventricle, the caudal artery, and the right atrium. Regional blood flows were determined by radioactive microsphere injection into the left ventricle with reference sampling from the caudal artery. Cardiac output (CO) was 289 ml . min-1 . kg in C and did not change with NG; however, in HCO systemic CO was decreased 31, 23, and 23% by NG from 350 ml . min-1 . kg. In both groups left ventricular end-diastolic pressure was reduced (C, 8.4–5.0; HCO, 19.8–12.7 mmHg); however, central venous pressure was reduced only in C (1.2–0.3 mmHg). During NG primarily at 2 and 8 micrograms/kg, arterial blood flow was lower and vascular resistance was higher in HCO compared with C in the following regions: kidney, ileum, jejunum, skin, heart, spleen, stomach, and testes, whereas no major differences were noted in the cerebellum, cerebrum, liver, or skeletal muscle. Thus acute NG infusion is a more potent regional vasodilator in C than in HCO. It is suggested that this difference is related to a more powerful NG-induced sympathetic reflex activation in the HCO group, which strongly attenuates the direct vasodilator effect of NG that was apparent in C.
Transthoracic defibrillation in 100-kg calves with sequentially applied pulses
Authors: Gold Jerry H. , Schuder John C. , Stoeckle Harry , McDaniel Wayne C. , Moellinger Duane W. , Roberts Stephanie A.
Published: December 2017

The effectiveness of up to five 50-A, 4-ms rectangular pulses (each nominally 50% successful) followed, when required, by up to six 70-A, 6-ms pulses applied at 15-s intervals in reversing ventricular fibrillation in 100-kg calves was studied in 600 episodes in which 50-A, 6-ms; 70-A, 3-ms; 70-A, 6-ms; 70-A, 12-ms; or 100-A, 6-ms prefibrillation shocks had been delivered 5 s before the induction of fibrillation and in another 600 episodes in which the prefibrillation shock was omitted. We found that 1) there was a modest adverse influence of the prefibrillation shock upon the outcome of the 50-A, 4-ms portion of the sequential shock effort; 2) the 50-A, 4-ms shocks remained reasonably successful throughout the five-shock sequence; 3) when the prefibrillation shock was omitted, the time intervals for a return of a ventricular complex and normal sinus rhythm in the postdefibrillation electrocardiogram increased rapidly with the number of shocks required for defibrillation; and 4) if defibrillation was not achieved with the five-shock sequence, a single 70-A, 6-ms shock was about 94% successful and the sequence of up to six shocks was 100% successful.

ventricular defibrillation; large-animal defibrillation; postdefibrillation arrhythmias; strength-duration success contours; sequential-shock strategy; single-shock strategy

Submitted on March 31, 1982

Accepted on July 23, 1982
Autonomic influences on atrioventricular conduction in conscious dogs
Authors: Thomas J. X. , Randall W. C.
Published: December 2017

Autonomic innervation of the atrioventricular (AV) junction modulates conduction of the cardiac impulse, the sympathetic nerves facilitating and parasympathetic nerves impeding conduction. Experiments assessed the relative importance of parasympathetic vs. sympathetic control by pharmacologic blockade with atropine (0.2 mg/kg) or propranolol (1.0 mg/kg) while pacing the right atrium (100-400 beats/min) in normal, conscious resting dogs and in dogs that had undergone chronic, intrapericardial cardiac denervation. Maximum pacing rate with 1:1 atrioventricular conduction was termed Rmax. Control Rmax at rest was 125.69 +/- 9.49 beats/min and was slightly reduced after propranolol to 118.28 +/- 10.98 (P = 0.043). After atropine, Rmax was significantly increased to 344 beats/min. Propranolol and atropine together resulted in an Rmax of 308 beats/min, which was significantly less than after atropine alone. Rmax in cardiac-denervated dogs was 301 beats/min, which was not significantly different from that following total pharmacologic blockade. In conscious, resting, unsedated dogs, the upper limit of AV nodal conduction is associated with the level of parasympathetic rather than sympathetic tone; during exercise the sympathetics assume greater importance.
Analysis of coronary collateral structure, function, and ischemic border zones in pigs
Authors: Patterson R. E. , Kirk E. S.
Published: December 2017

The purpose of this study was to compare coronary collateral structure and function in pigs with those in dogs and to analyze the distribution of collateral blood flow across the lateral and transmural border zones in the pig. After acute occlusion of the left anterior descending coronary artery (LAD) in 26 anesthetized open-chest pigs, minimal collateral blood flow was indicated by retrograde flow (0.2 +/- 0.1 ml/min) and microsphere-myocardial blood flow (0.005 +/- 0.001 ml X min-1g-1). Postmortem injection of the distal LAD followed by clearance of the heart demonstrated few tiny collateral structures and negligible collateral filling of other arteries. In contrast to dogs, pigs showed no measurable gradient of collateral blood flow across the transmural border zone, and pigs showed no change in collateral blood flow or its transmural distribution during retrograde drainage of collateral blood flow or elevated left ventricular filling pressures. Pigs showed higher myocardial blood flow in the lateral border than in the center of the ischemic zone. As in the dog, however, this gradient of blood flow across the lateral border zone was accounted for by overlap between occluded LAD branches and unoccluded coronary arterial branches rather than by preferential collateral perfusion of the lateral border of the ischemic zone. We conclude that the pig has a homogeneous distribution of collateral blood flow across the transmural and lateral border zones after acute coronary occlusion but that the minimal collateral circulation limits the usefulness of the pig as a model of ischemic heart disease.
Myocardial blood flow and function during gradual coronary occlusion in awake dog
Authors: Hill R. C. , Kleinman L. H. , Tiller W. H. , Chitwood W. R. , Rembert J. C. , Greenfield J. C. , Wechsler A. S.
Published: December 2017

The purpose of this study was to correlate dimensions and transmural blood flow in a segment of myocardium supplied by a coronary artery undergoing gradual closure. Nine adult dogs were instrumented with an electromagnetic flow probe, pneumatic occluder, and an ameroid constrictor on the circumflex coronary artery. Ultrasonic crystals were implanted 10 mm from the external surface of the left ventricle in a segment perfused by the circumflex artery. Regional blood flow was determined with 7- to 10-microns radiolabeled microspheres. Data were collected in the awake state at rest before closure began (control), during partial closure, and immediately after total closure. Seven of the nine animals were studied after occlusion during treadmill exercise. During both partial and total closure at rest the rate and extent of systolic shortening as well as the transmural blood flow were unchanged from control. During treadmill exercise mean flow increased. However, flow was redistributed away from the inner two layers causing deterioration in both the rate and extent of shortening of this segment. These data suggest that, although regional myocardial function and flow can be maintained at rest by the immature canine collateral circulation, these parameters are impaired markedly during augmented flow with exercise.
Influence of volume changes on osmolality-vasopressin relationships in conscious dogs
Authors: Quillen E. W. , Cowley A. W.
Published: December 2017

The relative importance of plasma osmolality (Posm) and left atrial pressure (LAP) as controllers of plasma vasopressin concentration (PAVP) was investigated in conscious dogs (n = 8). New techniques for the continuous measurement of LAP and computerized data collection permitted monitoring of LAP and mean arterial pressure (MAP) while Posm was suppressed with intravenous distilled water and then elevated with hypertonic NaCl. PAVP was determined by radioimmunoassay. This relationship between Posm and PAVP was determined at low, normal, and high (-0.9 +/- 0.8, 1.8 +/- 0.8, and 7.7 +/- 1.1 cmH2O, respectively) levels of LAP produced by either hemorrhage or autotransfusion of whole blood. MAP was not altered by these maneuvers. The results of these short-term studies have demonstrated a significant modulation of the osmoregulation of PAVP by changes in blood volume as indexed by LAP. Because of this modulation, PAVP is regulated so that contraction or expansion of the blood volume is more expeditiously corrected than would occur if osmoreceptors alone regulated plasma vasopressin.
Influence of central nervous system on arterial pressure during endotoxin shock
Authors: Janssen H. F. , Lutherer L. O.
Published: December 2017

Some investigators have suggested that the hypotensive effects of endotoxin are exerted at the level of central nervous system (CNS). Others feel the effects are exerted peripherally and that the CNS is involved in the regulation of the cardiovascular system during the shock state. Still other data suggest that endotoxin shock is entirely a peripheral phenomenon. The present study used ventriculocisternal perfusion of endotoxin, a pretrigeminal brainstem transection, two midcollicular decerebrate preparations, and Cushing's reflex to investigate the involvement of the CNS during endotoxin shock. The results suggest the following: 1) endotoxin perfused centrally at a concentration equivalent to the maximum obtainable after peripheral injection will not alter mean arterial pressure (MAP); 2) either the forebrain is not involved in the MAP response or the remaining regions can compensate for its absence; and 3) Cushing's reflex will block the initial endotoxin-induced hypotension.
Heart rate-independent energetics and systolic pressure-volume area in dog heart
Authors: Suga H. , Hisano R. , Hirata S. , Hayashi T. , Yamada O. , Ninomiya I.
Published: December 2017

Left ventricular (LV) systolic pressure-volume area (PVA), a new measure of total mechanical energy for the contraction, linearly correlates with its oxygen consumption per beat (VO2) regardless of contraction mode in a canine heart with stable chronotropism and inotropism. PVA is the area in the pressure-volume (PV) diagram circumscribed by the end-systolic and end-diastolic PV relation curves and the systolic segment of the PV loop and has dimensions of energy. We investigated whether primary changes in heart rate would affect the VO2-PVA relation. In the excised cross-circulated canine heart with left ventricular load controlled with a servo pump, we changed heart rate by pacing to compare the VO2-PVA relations at low [124 +/- 17 (SD) min-1] and high (193 +/- 23) heart rates. In 15 left ventricles, VO2 (ml O2 X beat-1 X 100 g LV-1) was (1.75 +/- 0.57) X 10(-5) PVA (mmHg X ml X beat-1 X 100 g LV-1) + 0.031 +/- 0.011 (ml O2 X beat-1 X 100 g LV-1). The VO2-PVA relation was virtually independent of heart rate in individual hearts. We conclude that the load-independent VO2-PVA relationship is not affected by chronotropism in a given canine left ventricle.
Abolition of digitalis tachyarrhythmias by caffeine
Authors: Di Gennaro M. , Valle R. , Pahor M. , Carbonin P.
Published: December 2017

Digitalis-induced ventricular tachyarrhythmias (VTAs) are believed to be due to oscillatory afterpotentials (OAPs) generated by an oscillatory release of calcium from the sarcoplasmic reticulum (SR). Caffeine blocks the calcium uptake into the SR and then may influence VTAs by depleting the SR stores of calcium. We studied the action of digitalis and caffeine, singly and in combination, in the isolated guinea pig heart perfused by means of a modified Langendorff apparatus. Digitalis (beta-methyldigoxin 1.27 X 10(-6) M) caused VTAs and ventricular fibrillation (VF) in all the hearts. Caffeine alone decreased heart rate but never caused VTAs. With the administration of digitalis and caffeine (1 mM), VTAs rarely developed and VF never occurs. With digitalis and higher concentration of caffeine (10 mM), neither VTAs nor VF were observed. In hearts with complete atrioventricular block, digitalis increased the ventricular rate from 143 +/- 10 to 270 +/- 13 beats/min (n = 8) in 12 +/- 1.9 min and provoked the appearance of multiple ventricular pacemakers. The addition of 10 mM caffeine to the digitalis-containing solution reduced the ventricular rate to 171 +/- 12 beats/min (P less than 0.001 vs. digitalis alone, not significant vs. control, n = 8) and abolished the digitalis-induced multiple pacemakers. Ventricular asystole was occasionally observed during the perfusion with digitalis + 10 mM caffeine. Caffeine alone did not modify the diastolic pressure, whereas caffeine and digitalis rapidly increase it. These results represent indirect evidence to support that SR plays an important role in the origin of the digitalis-induced VTAs.
Dietary linoleic acid deprivation: effects on blood pressure and PGI2 synthesis
Authors: Dusing R. , Scherhag R. , Glanzer K. , Budde U. , Kramer H. J.
Published: December 2017

The possible role of arachidonic acid metabolites in the regulation of arterial blood pressure was investigated in rats receiving 0, 5, or 9 energy (en) % linoleic acid in their diet (groups 1-3) over 6 wk. In group 1 animals, systolic arterial blood pressure significantly increased from 100.5 +/- 2.0 to 110.6 +/- 3.1 mmHg (P less than 0.01) after 6 wk of dietary linoleic acid deprivation, whereas no effect on blood pressure was observed in group 2 and 3 animals receiving dietary linoleic acid supplements. Generation of prostacyclin (PGI2)-like activity by isolated aorta from rats fed the different diets was determined using a platelet-aggregation bioassay following incubation of aortic tissue for 12, 15, and 30 min, respectively. In isolated aorta from rats fed the 5 en% linoleic acid, production of PGI2 was 55.9 +/- 1.2, 70.5 +/- 2.6, and 90.9 +/- 3.6 pmol/mg over the three incubation periods. In group 1 animals, a significant suppression of PGI2 generation to 35.4 +/- 1.5, 41.1 +/- 1.7, and 55.0 +/- 1.2 pmol/mg (P less than 0.005) was observed, whereas PGI2 production was unaltered in aortic tissue from group 3 animals. In contrast, plasma concentrations of circulating thromboxane B2 were highest in group 1 animals (2.15 +/- 0.38 pmol/ml) and measured 1.28 +/- 0.17 and 0.83 +/- 0.10 pmol/ml in group 2 and 3 animals, respectively. Our results demonstrate that dietary deprivation of the arachidonic acid precursor linoleic acid increases arterial blood pressure that is associated with a suppression of vascular PGI2 synthesis and, most likely, a secondary rise in circulating thromboxane concentrations.