bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional development of the creatine kinase system in perinatal rabbit heart.
Authors: Hoerter J A , Kuznetsov A , Ventura-Clapier R
Published: June 2012

The functional development of the creatine kinase system has been studied in rabbit heart during perinatal growth. Fiber bundles were obtained from left ventricles of fetal rabbits at the 30th day of gestation, newborn rabbits aged 1, 3, 8, and 17 days, and adult rabbits. Total creatine kinase activity was constant during perinatal development, whereas myofibrillar bound creatine kinase activity increased 15-fold during the first postnatal week. Functional activity of myofibrillar creatine kinase was assayed in Triton X-100-skinned fibers by its ability to induce active tension in the absence of ATP or to relax rigor tension. It was very low in 1-day-old newborns and increased during the first 2 weeks to reach adult levels 17 days after birth. Functional activity of mitochondrial creatine kinase was determined in saponin-skinned fibers. Creatine-stimulated respiration appeared only after birth and increased gradually between 1 and 17 days after birth. The results show that, although the two creatine kinase isoforms (mitochondrial and myofibrillar) are expressed at different stages during development, their functional activities appear in parallel in mitochondria and myofibrils. Early postnatal development is characterized by binding of creatine kinase isoenzymes to intracellular organelles. Such compartmentation participates in the postnatal cardiac cellular maturation.
Diastolic anisotropic properties of the left ventricle in the conscious dog.
Authors: Olsen C O , Glower D D , Lee K L , McHale P A , Rankin J S
Published: June 2012

The role of myocardial anisotropy in determining change in left ventricular shape during diastolic filling has not yet been demonstrated. Therefore, 11 conscious dogs were instrumented with global ultrasonic dimension transducers to measure left ventricular major and minor axis diameters and equatorial wall thickness. Myocardial geometry was represented as a three-dimensional ellipsoidal shell. Left ventricular transmural pressure was measured with micromanometers, and ventricular volume was varied by inflation of vena caval occluders. Left ventricular wall strains and stresses calculated from the ellipsoidal shell model agreed closely with those measured directly by myocardial force and dimension transducers. Unequal normalized diastolic stress-strain relations were observed in the latitudinal, longitudinal, and wall thickness directions, reflecting anisotropic mechanical properties of the myocardium. Although a greater wall stress in the latitudinal versus longitudinal axis was predicted adequately from left ventricular geometry alone, the observed latitudinal strain exceeded longitudinal strain by an amount greater than was predicted by geometric considerations alone, suggesting that myocardial anisotropy contributes significantly to changes in ventricular shape during diastolic filling.
Distribution of carbon flux within fatty acid utilization during myocardial ischemia and reperfusion.
Authors: Nellis S H , Liedtke A J , Renstrom B
Published: June 2012

Twenty-nine intact, working pig hearts were extracorporeally perfused and divided into two study groups (16 Aerobic and 13 Ischemic/Reflow hearts). Step function, equilibrium labeling with [14C]palmitate was used to develop uptake and washout curves of radioactive fatty acid products contained in coronary effluent during either aerobic perfusion or reperfusion after ischemia (60% reduction in left anterior descending coronary flow for 30 minutes). Left anterior descending control flows were slightly overperfused in Aerobic hearts (18% higher than in Ischemic/Reflow hearts); otherwise, circumflex and right coronary flows, left ventricular pressure, and serum fatty acids and blood sugar levels were comparable between groups. As expected in Ischemic/Reflow hearts, recovery of regional systolic shortening and myocardial oxygen consumption in reperfusion was only modestly impaired (-20% and -19%, respectively, not significant and p less than 0.011 compared with preischemic values, not significant from Aerobic hearts). The only significant metabolized product to be released from labeled fatty acid utilization in either group was 14CO2. A smaller fatty acid pool also was measured and accounted for by that contained in the coronary intravascular volume. We could determine no significant back diffusion of fatty acids from myocardium in either perfusion condition. Uptake time constants of the early phase of 14CO2 production also were virtually identical in both groups (19.9 +/- 3.2 versus 16.7 +/- 3.2 minutes in Aerobic and Ischemic/Reflow hearts, respectively) and strongly correlated with hemodynamics as described by heart rate. In washout studies, tissue radioactivity in the aqueous soluble and fatty acid pools declined in both study groups, and counts in complex lipids and cholesterol/cholesteryl esters remained steady, whereas those in triacylglycerols varied. Washout of 14CO2 in both groups never reached background radioactivity over a 40-minute sampling after cessation of isotope infusion into the perfusate, suggesting slow release of trapped substrate from intracellular pools, which then proceeded to fatty acid oxidation. In conclusion, these experiments have demonstrated very similar findings with respect to fatty acid uptake, storage, and release characteristics between aerobic and reperfused myocardium. We found no differences in preferred substrate utilization and oxidation as a result of reversible ischemia followed by reflow.
Spontaneous tachyarrhythmias after cholinergic suppression in the isolated perfused canine right atrium.
Authors: Schuessler R B , Rosenshtraukh L V , Boineau J P , Bromberg B I , Cox J L
Published: June 2012

Atrial fibrillation occurs spontaneously after bradycardia induced by acetylcholine infusion or vagal stimulation. To determine the mechanism of initiation of this tachyarrhythmia, we infused acetylcholine (5 ml, 10(-3.5) M) into Krebs-Henseleit-perfused isolated canine right atria (n = 10). Unipolar electrograms were recorded from 250 sites simultaneously during control rhythms, pacing (cycle length = 300 msec) with and without acetylcholine, and recovery of spontaneous activity. Activation sequence maps were constructed from each recording. Stable spontaneous rhythm was present in all preparations during control conditions. Activation sequence maps, recorded during continuous pacing with and without acetylcholine, demonstrated no dromotropic changes due to the acetylcholine. Focal asynchronous recovery of spontaneous activity was initiated from different sites, resulting in bigeminal or trigeminal premature depolarizations in 41 of 73 cases after infusion of acetylcholine. A reentrant tachyarrhythmia was initiated in 24 of 41 cases by the closely coupled recovery beats (A1A2 = 100 +/- 37 msec; A2A3 = 97 +/- 27 msec). The reentry was initiated by interaction of the premature impulse with regions of functional block that were a result of the cholinergically induced dispersion of refractoriness. All the tachyarrhythmias terminated spontaneously, and stable spontaneous control rhythms returned. In conclusion, the data suggest that the premature depolarizations that initiate the reentrant tachyarrhythmia are caused by the asynchronous recovery of multiple right atrial pacemakers accompanied by variable entrance block at the later depolarizing sites.
Effects of epinephrine on firing characteristics of two functionally different types of carotid baroreceptors.
Authors: Seagard J L , van Brederode J F , Dan C , Hopp F A , Elegbe E O , Gallenberg L A , Kampine J P
Published: June 2012

Sympathetic stimulation and catecholamine exposure have been shown to sensitize the arterial baroreceptors, but the extent or importance of this effect is not known. We performed this study to investigate the effects of sympathetic feedback on the carotid sinus baroreceptors, specifically examining the effect of the stimulation on the two different functional types of baroreceptors characterized in an earlier study. The existence of two baroreceptor function-response curves has suggested that the roles of the two functionally different baroreceptors may not be the same. If true, the effects of epinephrine exposure on baroreceptor firing characteristics may contribute to differential roles played by each baroreceptor type in the control of blood pressure. Single-fiber baroreceptor activity from a vascularly isolated carotid sinus was recorded during slow increases in carotid sinus pressure before and during exposure to epinephrine (10(-8) to 10(-6) M). Baroreceptor firing characteristics were determined from function curves plotting carotid sinus pressure versus nerve activity, with curve-fitting analysis of the hyperbolic type I and sigmoidal type II baroreceptor curves used to obtain threshold (Pth) and saturation (Psat) pressures, threshold (Fth) and saturation (Fsat) firing rates, and sensitivity (slope) for each baroreceptor before and during epinephrine exposure. The possible mechanisms of observed changes were examined using our previously published baroreceptor computer model. Epinephrine exposure was found to significantly increase sensitivity, Fth, and Fsat of both types of baroreceptors, with a relatively greater effect on type I sensitivity and on type II Fth and Fsat. Epinephrine also was found to increase the level of spontaneous discharge for type II baroreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of neuropeptide Y on cell length and membrane currents in isolated guinea pig ventricular myocytes.
Authors: Bryant S M , Ryder K O , Hart G
Published: June 2012

Direct effects of neuropeptide Y were studied in left ventricular myocytes isolated from guinea pigs. Contraction was measured as the change in unloaded cell length using a photodiode array. Action potentials were elicited at 1 Hz in current-clamp mode, and membrane currents were measured using a switch-clamp amplifier with 2 M-KCl microelectrodes. At concentrations of 10(-6) M and above, neuropeptide Y reduced contraction in a concentration-dependent fashion. The reduction in contraction by the peptide was proportionately greater in the presence of isoproterenol, and the increase in contraction caused by isoproterenol was completely inhibited by 10(-6) M neuropeptide Y. In response to neuropeptide Y, action potential duration was shortened, and the time course of the shortening was similar to that of the reduction in contraction. Under voltage clamp, 1 x 10(-5) M neuropeptide Y reduced peak L-type calcium current by 32% and shifted the myocyte current-voltage relation during a slow ramp in a manner that suggested a reduction in the background rectifier K+ current. The effects of the peptide on membrane currents were greatly attenuated by preincubation of the cells with pertussis toxin (100 ng/ml). We conclude that neuropeptide Y reduces developed shortening, action potential duration, L-type calcium current, and background rectifier current in single guinea pig ventricular myocytes and that these effects are mediated, at least in part, via membrane G proteins.
Evidence for functional alpha 2-adrenoceptors on vascular sympathetic nerve endings in the human forearm.
Authors: Grossman E , Chang P C , Hoffman A , Tamrat M , Goldstein D S
Published: June 2012

The role of alpha 2-adrenoceptors on vascular sympathetic nerve endings in modulating release of the sympathetic neurotransmitter norepinephrine (NE) in humans was examined by measuring the regional rate of appearance of NE in forearm venous plasma (forearm NE spillover [FSO]) in 32 healthy volunteers during intra-arterial infusion of drugs acting at adrenoceptors or directly on vascular smooth muscle. Simultaneous intra-arterial infusions of tracer amounts of [3H]NE were used to calculate the extraction rate of NE in the forearm. Methoxamine or propranolol with epinephrine (PRO + EPI) was used to stimulate alpha-adrenoceptors, yohimbine was used to inhibit alpha-adrenoceptors, and sodium nitroprusside (NIP) was used to produce increases in forearm blood flow directly. Sympathetic efferent activity was manipulated by systemic intravenous infusions of NIP or trimethaphan. Yohimbine and NIP increased and PRO + EPI and methoxamine decreased NE FSO, without effects on systemic blood pressure, heart rate, or arterial levels of catechols. Changes in FSO were flow dependent; therefore, the slope of the relation between the changes in FSO and forearm blood flow was used to evaluate the effects of each drug on regional sympathoneural activity. During administration of yohimbine, the mean slope of the relation between the change in estimated FSO and the change in forearm blood flow was about four times that of the mean slope during administration of NIP (F = 6.35, p less than 0.05). The slopes of the relations between changes in FSO and forearm blood flow were unaffected by systemic trimethaphan or NIP infusion, indicating that the activity of alpha 2-adrenoceptors was not altered during inhibition or reflexive stimulation of sympathetic outflow. The results suggest that alpha 2-adrenoceptors modulate release of NE from vascular sympathetic nerve endings in humans and that the function of these receptors is unchanged during acute changes in junctional NE concentrations.
EMD 53998 sensitizes the contractile proteins to calcium in intact ferret ventricular muscle.
Authors: Lee J A , Allen D G
Published: June 2012

EMD 53998 (a thiadiazinone) is an inotropic drug that produces a pronounced increase in the Ca2+ sensitivity of the contractile proteins in skinned cardiac fibers. The present study was undertaken to determine whether this effect on Ca2+ sensitivity could explain the increase in tension observed in intact ventricular muscle. The experiments were performed on isolated ferret papillary muscles that had been microinjected with aequorin to measure the intracellular Ca2+ concentration. Force and intracellular Ca2+ concentration were monitored before, during, and after application of EMD 53998. EMD 53998 (5 microM) increased developed tension by 230%; aequorin light transients increased by only 85%, and this increase was reduced and became insignificant in the presence of agents that prevent catecholamine release. When a similar increase in developed tension was produced by elevation of extracellular calcium, the aequorin light transients increased by 240%. Thus, EMD 53998 produces a substantial Ca2+ sensitization in intact ventricular muscle, and this can explain most of its inotropic effect. In addition, EMD 53998 caused a small prolongation of the time course of contraction and a small reduction of the time course of the aequorin light transient. A computer model is described that shows that both these effects can be explained by the effect of EMD 53998 on Ca2+ sensitivity. At much higher concentrations, EMD 53998 also caused an increase in resting tension. EMD 53998 is the first agent for which much of the inotropic effect in intact cardiac muscle can be accounted for by increased Ca2+ sensitivity of the contractile proteins. Inotropic agents with this mechanism of action cause increased force production with much less increase in the intracellular Ca2+ transients than conventional agents and, therefore, increase the energy efficiency of the myocardium and are less likely to cause Ca(2+)-activated arrhythmias.
In vivo demonstration of cardiac beta 2-adrenoreceptor sensitization by beta 1-antagonist treatment.
Authors: Hall J A , Petch M C , Brown M J
Published: June 2012

Treatment with beta 1-selective antagonists causes selective sensitization of isolated strips of human atrial myocardium to the inotropic action of epinephrine and beta 2-agonists but not of norepinephrine. To determine whether beta 1-selective antagonist treatment alters the responsiveness of cardiac beta 2-adrenoreceptors in vivo, we measured the positive chronotropic responses to salbutamol injected into the right coronary artery. Ten patients treated with atenolol (50-100 mg daily) were compared with 10 patients not treated with beta-blockers. The mean dose required to cause an increase in heart rate of 30 beats/min was 2.29 micrograms (log dose 0.36 +/- 0.12 micrograms [mean +/- SEM]) in the atenolol-treated patients. In the non-beta-blocker-treated patients, the dose required to cause an increase in heart rate of 30 beats/min was significantly greater, 8.91 micrograms (log dose 0.95 +/- 0.11 micrograms) (p less than 0.005). We conclude that treatment with beta 1-selective beta-blockers leads to increased cardiac responsiveness to beta 2-adrenoreceptor stimulation. This may be the underlying mechanism of the beta-blocker withdrawal syndrome and may make the heart more susceptible to the adverse effects of epinephrine in situations of stress (e.g., myocardial infarction).
Increased oxygen cost of contractility in stunned myocardium of dog.
Authors: Ohgoshi Y , Goto Y , Futaki S , Taku H , Kawaguchi O , Suga H
Published: June 2012

Recent studies have shown that myocardial oxygen consumption does not proportionally decrease with the deterioration of contractile function in stunned myocardium. To investigate this disproportion, we studied the end-systolic pressure-volume relation and the relation between oxygen consumption per beat (VO2) and systolic pressure-volume area (PVA, a measure of total mechanical energy) in stunned hearts. In the VO2-PVA relation, VO2 can be divided into PVA-dependent and PVA-independent fractions. In excised cross-circulated dog left ventricles, a 15-minute normothermic global ischemia followed by 60-120 minutes of reperfusion significantly decreased the ventricular contractility index (Emax) by approximately 40%, but the PVA-independent VO2 did not significantly decrease. Oxygen cost of PVA, defined as the slope of the VO2-PVA relation, was slightly decreased in stunned hearts. Restoration of the depressed Emax to the preischemic control level by calcium infusion increased the PVA-independent VO2 to 137 +/- 27% of control level (p less than 0.01). Oxygen cost of contractility, defined as the slope of the relation between PVA-independent VO2 and Emax, increased from 0.0011 +/- 0.0003 to 0.0023 +/- 0.0005 ml O2.ml.mm Hg-1.beat-1 per 100 g myocardium in control and stunned hearts, respectively (p less than 0.01). From these new finding, we conclude that the unchanged VO2, despite the depressed contractility in stunned myocardium, is mainly due to the increased oxygen cost of contractility.
Polymorphonuclear neutrophil contribution to induced tolerance to bacterial lipopolysaccharide.
Authors: Barroso-Aranda J , Schmid-Schönbein G W , Zweifach B W , Mathison J C
Published: June 2012

The objective of this study was to investigate mechanisms by which polymorphonuclear neutrophils (PMNs) contribute to the tolerance induced by repeated lipopolysaccharide (LPS) injections. Tolerance was developed by daily intraperitoneal injections of sublethal doses of LPS for 4 days (LPS-tolerant group); controls were not pretreated (LPS-control group). Both groups were challenged with 9 mg/kg i.v. Escherichia coli LPS, a dose that resulted in 25% survival in LPS-control rats compared with 100% survival in LPS-tolerant rats. LPS injection caused an initial neutropenia in both groups. The neutropenia persisted throughout the experiment in LPS-control rats, whereas in LPS-tolerant rats the circulating PMN count increased dramatically; after 6 hours, the PMN count was 16-fold higher than that in LPS-control rats. Activation of circulating PMNs, PMN adhesion to nylon fibers, and tumor necrosis factor/cachectin activity were all increased in control rats given LPS. In contrast, LPS-tolerant rats had low activation of circulating PMNs, no trend for PMN adhesion to nylon fibers, and markedly reduced tumor necrosis factor activity. To determine whether neutropenia was associated with a trapping of PMNs in the microcirculation, we used a carbon perfusion technique 6 hours after LPS injection and examined histological sections of the myocardium. All of the arterioles and venules in both groups contained carbon; only capillaries showed evidence of obstruction. A significantly higher percentage of obstructed capillaries was observed in LPS-control rats than in LPS-tolerant rats. Obstruction of capillaries was consistently associated with trapped leukocytes. We conclude that PMN cytotoxicity induced by LPS involves microcirculatory entrapment and activation of PMNs. Repeated LPS pretreatment reduces dramatically circulating PMN activation and adhesion and is associated with an elevated circulating PMN count, a low degree of microvascular plugging, and survival after a normally lethal dose of LPS.
Preservation of venular but not arteriolar smooth muscle alpha-adrenoceptor sensitivity during reduced blood flow.
Authors: Muldowney S M , Faber J E
Published: June 2012

To compare arteriolar versus venular smooth muscle sensitivity to myogenic and metabolic inhibition during reduced blood pressure and flow, we measured the diameter of first-order venules (diameter, 230 microns) and arterioles (diameter, 156 microns) of the denervated, blood-perfused rat cremaster skeletal muscle that was suspended in a tissue bath. Sensitivity was determined for bath-added norepinephrine in the presence of yohimbine or prazosin to produce alpha 1- and alpha 2-adrenoceptor constriction, respectively, and for KCl to examine non-receptor-mediated sensitivity. To reduce venular pressure and flow, vasopressin, which constricts cremaster arterioles but not venules, was applied locally at a maximally effective concentration. This arteriolar constriction had no effect on venular sensitivity to alpha 1-adrenoceptor and KCl-mediated constriction. Venular sensitivity (-log M EC50) to alpha 1 and to KCl activation was 6.20 +/- 0.10 and 1.20 +/- 0.04 in the absence and 6.34 +/- 0.09 and 1.30 +/- 0.03 in the presence of arteriolar constriction, respectively. Venular sensitivity to alpha 2 activation was actually greater during arteriolar constriction (6.25 +/- 0.11 in the absence of constriction versus 7.06 +/- 0.13 in the presence of constriction, p less than 0.001). In a second series, the effect of reduced cremaster perfusion pressure and flow on both arteriolar and venular sensitivity was examined by mechanically lowering cremaster inflow. Reduction of first-order arteriolar and venular flow by 82-85% attenuated arteriolar alpha 1 and abolished alpha 2 sensitivity but had no effect on venular adrenergic sensitivity; KCl sensitivity was increased. These data indicate that, in contrast to arteriolar smooth muscle, venular smooth muscle alpha-adrenoceptor sensitivity is preserved during reduced pressure and flow and, thus, is little affected by metabolic and myogenic regulation. The selective depressant effect on arteriolar adrenergic but not KCl constriction suggests that myogenic/metabolic inhibition of arterioles is receptor specific.
Dynamics of the background outward current of single guinea pig ventricular myocytes. Ionic mechanisms of hysteresis in cardiac cells.
Authors: Delmar M , Ibarra J , Davidenko J , Lorente P , Jalife J
Published: June 2012

Subthreshold potentials are thought to be mediated by time-independent, "passive" background currents. In this study, we show that the background current-voltage (I-V) relation of guinea pig ventricular myocytes is changed significantly by repetitive stimulation, in such a way that cell excitability becomes enhanced. Myocytes were used for whole-cell voltage-clamp experiments. A voltage-clamp ramp (100 mV/sec) to -50 mV was applied from a holding potential of -100 mV. Subsequently, a train of square voltage-clamp pulses to +10 mV (duration, 300 msec; interpulse interval, 300 msec) was delivered from a holding potential of -85 mV. A new ramp was applied again immediately after the train, and the resulting I-V curve was compared with that obtained before the train. Pulsing displaced the I-V relation to the right, the zero-current point becoming 1-2 mV less negative, and increased the degree of inward-going rectification. These changes were insensitive to tetrodotoxin (30 microM); disappeared during superfusion with cobalt (2 mM), verapamil (22 microM), or ryanodine (5 microM); and could not be mimicked by agonists of the protein kinase C system. In the presence of cesium (8 mM), pulsing still displaced the I-V curve to the right. However, the linear portion of the curve became steeper after the train. Subtraction of the cesium-sensitive current from control revealed that, although the zero-current point remained constant, the I-V relation showed a stronger inward-going rectification after pulsing. In accordance with these results, we have demonstrated hysteresis of excitability in ventricular myocytes. We conclude that the observed changes are mediated by an increase in intracellular calcium, which leads to an increase in rectification of IK1, as well as to activation of another membrane-conductance system, perhaps the Na-Ca exchange or the Ca(2+)-activated, nonselective current.
Reactivity of canine isolated epicardial collateral coronary arteries. Relation to vessel structure.
Authors: Angus J A , Ward J E , Smolich J J , McPherson G A
Published: June 2012

To study the relation between structure and vascular reactivity in mature coronary collateral arteries, we prepared 17 dogs with a casein occluder near the origin of the circumflex coronary artery. At least 24 weeks later, we examined the reactivity of surface collateral arteries (approximately 500 micron i.d.) to a range of constrictor and dilator agents and compared them with normal left anterior descending coronary arteries of similar size branching away from the collateral zone. Pairs of normal and collateral arteries 2 mm long were mounted in a double-vessel myograph for isometric force recording. Arteries were contracted by K+ (124 mM) or by cumulative addition of endothelin-1 (1-100 nM) or U46619 (1-300 nM), a thromboxane A2 mimetic drug. In each case, the collateral vessels contracted to approximately half the force generated by the normal arteries. When partially contracted by K+ (25-30 mM), the collateral vessels had a greater range of relaxation and similar sensitivity to acetylcholine, sodium nitroprusside, and cromakalim compared with normal arteries. Morphological and morphometric analyses revealed that the collateral arteries had thickened adventitia, thinner media, ruptured internal elastic laminae, and a thick neointima lined by endothelium. Theoretical calculations of luminal area were made for isotonic conditions in response to constrictor stimuli. Despite the poor contractility of the collateral arteries, the neointimal luminal encroachment further reduced the lumen to zero, an exaggerated response compared with normal arteries. Coronary collateral arteries are thus compromised flow conduits that may play a role in vasospastic angina.
Troponin I isoform expression in human heart.
Authors: Hunkeler N M , Kullman J , Murphy A M
Published: June 2012

Troponin I is the inhibitory component of troponin, the thin filament regulatory complex in striated muscle. Separate genes encode cardiac-specific fast and slow skeletal-specific isoforms of this protein. We have previously described gene switching from the slow skeletal to the cardiac troponin I mRNA expression in developing rat heart. The purpose of this work was to characterize the expression of the different troponin isoforms in the human heart. Human cardiac and slow skeletal troponin I cDNA probes were obtained by screening an adult cardiac cDNA library and by Taq polymerase amplification of RNA from an infant's heart, respectively. We found that the cardiac troponin I isoform is tissue-specific in its expression in normal adult tissues. RNA blot analysis of cardiac ventricular RNA from infants with congenital heart disease and from an adult with cardiomyopathy revealed expression of human cardiac troponin I in all analyzed specimens. In addition, we found expression of slow skeletal troponin I mRNA and protein in infant hearts but no detectable mRNA expression in the adult heart. We conclude that troponin I isoforms are developmentally regulated in the human heart by a mechanism similar to that in the rat heart.
Isovolumic loading prevents atrophy of the heterotopically transplanted rat heart.
Authors: Klein I , Hong C , Schreiber S S
Published: June 2012

Heterotopically (infrarenal) transplanted cardiac isografts are histologically normal, spontaneously beating, hemodynamically unloaded hearts that undergo rapid and predictable atrophy. To study the factors that regulate cardiac growth we examined the effect of left ventricular (LV) isovolumic balloon placement on the weight, in vitro protein synthesis rate, and LV RNA content of the transplanted heart. At day 0 the donor LV weight was 367 +/- 8 mg, which decreased to 226 +/- 14 mg (p less than 0.001) after transplantation. Isovolumic loading with a latex balloon (volume, 111 +/- 10 microliters) significantly increased the LV weight of the transplanted heart to 397 +/- 13 mg when compared with that of the unloaded heart 14 days after surgery and prevented the atrophy when compared with the LV weight at day 0. Sham-loaded transplants had LV weights of 256 +/- 17 mg, which did not differ from the LV weight of unloaded transplanted hearts. Protein synthesis rates (nmol lysine/LV/hr) and total LV RNA and LV 18S RNA content were significantly greater in the balloon-loaded hearts when compared with the unloaded isografts and returned to levels similar to those measured in the in situ hearts. The ability of isovolumic loading of the LV to prevent atrophy via increased protein synthesis and the maintenance of LV RNA in the heterotopically transplanted heart further supports the important role of cardiac work in the regulation of cardiac growth.
Low-pressure-sensitive baroreceptor fibers recorded from rabbit carotid sinus nerves.
Authors: Qu L , Stuesse S L
Published: June 2012

Activity was recorded from physiologically identified baroreceptor or chemoreceptor fibers in carotid sinus nerves of urethane-anesthetized spontaneously breathing rabbits. A carotid sinus area was vascularly isolated so that carotid sinus pressure and perfusion medium (Locke's solution or rabbit blood) could be controlled. The cervical sympathetic, vagus, and aortic depressor nerves were bilaterally cut to eliminate vagal and cardiopulmonary reflexes. Baroreceptor fibers could be divided into two groups: fibers with a mean firing threshold of 47.6 +/- 1.9 mm Hg and no activity below this threshold (37 fibers) and fibers that were active at low intrasinus pressures (18.1 +/- 2.2 impulses/sec at an intrasinus pressure of 0 mm Hg). The baroreceptor fibers that were spontaneously active at low pressures were also chemically sensitive: discharge rate was increased by 5-hydroxytryptamine (10 fibers, p less than 0.01), nicotine (10 fibers, p less than 0.01), or hypercapnia (13 fibers, p less than 0.001). The activity of baroreceptor fibers with a clear pressure threshold was usually decreased by hypercapnia (26 of 27 fibers, from 18.8 +/- 3.1 to 13.2 +/- 3.9 impulses/sec). Chemoreceptor fibers failed to respond to intrasinus pressure changes from 0 to 100 mm Hg (n = 25 fibers, p greater than 0.5) but were sensitive to chemical changes, as expected. Thus, there is a subset of baroreceptor fibers that, under certain conditions, is spontaneously active at very low intrasinus pressures and responds to changes in the chemical milieu.
Inositol trisphosphate promotes Na-Ca exchange current by releasing calcium from sarcoplasmic reticulum in cardiac myocytes.
Authors: Gilbert J C , Shirayama T , Pappano A J
Published: June 2012

An early inward tail current evoked by membrane depolarization (from -80 to -40 mV) sufficient to activate sodium but not calcium current was studied in single voltage-clamped ventricular myocytes isolated from guinea pig hearts. Like forward-mode Na-Ca exchange, this early inward tail current required [Na+]o and [Ca2+]i and is thought to follow earlier reverse-mode Na-Ca exchange that triggers Ca2+ release from sarcoplasmic reticulum. The dependence of the early inward tail current on [Ca2+]i was supported by the ability of small (+10 mV) and large (+80 mV) voltage jumps from -40 mV to decrease and increase, respectively, the size of early inward tail currents evoked by subsequent voltage steps from -80 to -40 mV. As expected, tetrodotoxin selectively inhibited the early inward tail current but not the late inward tail current that followed voltage jumps to +40 mV test potentials. Although tetrodotoxin also blocked the fast Na+ current, replacement of extracellular Na+ by Li+ sustained the fast Na+ current. However, Li+, which does not support Na-Ca exchange, reversibly suppressed both the early and late inward tail currents. Inhibitors (ryanodine and caffeine) and promoters (intracellularly dialyzed inositol 1,4,5-trisphosphate) of sarcoplasmic reticulum Ca2+ release decreased and increased, respectively, the magnitude of the early inward tail current. The results substantiate the hypothesis that Ca2+ release from the sarcoplasmic reticulum participates in early Na-Ca exchange current and demonstrate that inositol 1,4,5-trisphosphate, by releasing Ca2+ from the sarcoplasmic reticulum, can promote Na-Ca exchange across the plasma membrane.
Effects of Experimental Coarctation of the Aorta on the Blood Pressure of Sheep
Authors: MAGAREY F. R. , STEHBENS W. E. , SHARP ALAN
Published: June 2012

Blood pressures have been taken from the carotid and femoral artery in sheep following experimental coarctation of the aorta at about the level of the ligamentum arteriosum. Systolic, diastolic, mean, and pulse pressures have been recorded at intervals of from 3 to 6 months over a period of as long as 3 years in some cases. Unoperated sheep have been used as controls. The main changes are a rise in all the carotid pressures and in the femoral diastolic, a fall in the femoral systolic and pulse pressures, and no significant change in the femoral mean pressure. These changes in hemodynamics resulting from coarctation may be adequately explained by the mechanical effects of the coarctation. Over a period of 3 years there is a slight rise of blood pressures in both the normal and the coarctated sheep.
An Experimental Study of the Effect of Chronic Atelectasis on Pulmonary and Bronchial Blood Flow
Authors: PETERS RICHARD M. , LORING WILLIAM E. , SPRUNT WILLIAM H.
Published: June 2012

Four dogs and one patient with uncomplicated atelectasis of an entire lung were studied. Arterial oxygen saturations were nearly normal, indicating diminished flow to the atelectatic lung. Angiography confirmed this finding. Vinyl plastic injections showed no evidence of increased bronchial collateral circulation and pathological examination of the atelectatic lung did not demonstrate any bronchiectasis.
Serum Activity Patterns of Glutamic Oxaloacetic Transaminase, Glutamic Pyruvic Transaminase and Lactic Dehydrogenase Following Graded Myocardial Infarction in Dogs
Authors: RUEGSEGGER PAUL , NYDICK IRWIN , FREIMAN ALVIN , LADUE JOHN S.
Published: June 2012

Following experimental myocardial infarction in the dog elevations of serum levels of glutamic-oxaloacetic transaminase (SGO-T), glutamic-pyruvic transaminase (SGP-T) and lactic dehydrogenase (SLD) were consistently noted in decreasing order. Evidence is presented that leakage into the serum from the damaged myocardium plays an important role in these elevations. This concept is supported by analyses of original tissue to blood enzyme concentration gradients, activities of homogenates of infarcts of varying ages, simultaneous measurements of coronary sinus and peripheral venous blood following infarction and contrasting results in man and the dog following infarction.
Further Observations on the Potentiation of Postnephrectomy Hypertension of the Dog by Dietary Protein
Authors: MUIRHEAD E. E. , STIRMAN J. A. , JONES F.
Published: June 2012

An assay procedure for the evaluation of dietary factors in renoprival hypertension over a short period is described. By means of this procedure dietary protein was found to potentiate renoprival hypertension of the dog. In the absence of dietary protein 2.5 mEq. sodium per kilogram per day was attended by a slight but significant elevation in the arterial pressure. The same level of hypertension was observed with fluid and sodium loading alone, dietary protein plus a lesser sodium intake, and dietary protein plus a greater sodium intake.
The Pulmonary Circulation Following Pneumothorax and Vagotomy in Dogs
Authors: SIMMONS DANIEL H. , HEMINGWAY ALLAN
Published: June 2012

Induction of pneumothorax in anesthetized dogs with a volume of air equal to the functional residual capacity does not lead to any immediate change in pulmonary artery or vein pressures or the pressure gradient. Cardiac output drops and pulmonary vascular resistance is elevated. This change in pulmonary resistance is essentially unaffected by vagotomy and is likely a mechanical effect of decreasing lung volume. Vagotomy alone leads to a decrease in cardiac output and an increase in pulmonary vascular resistance, possibly also because of mechanical effects.
Observations Concerning Both the Induction and the Regression of Lipid and Cholesterol Infiltration in Ocular Implants of Rabbit Aorta
Authors: FRIEDMAN MEYER , BYERS SANFORD O.
Published: June 2012

Segments of both normal and atherosclerotic rabbit aortas were placed in the anterior chamber of host rabbits according to the Higginbotham technic. Normal aorta segments placed in the eyes of cholesterol fed rabbits quickly became infiltrated with fat and cholesterol. The intensity of this infiltration exceeded that observed in the host's own aorta. Atherosclerotic aorta segments placed in the eyes of normal rabbits quickly lost both lipid and cholesterol.
Arterial Wall Potassium in Renal Hypertensive Rats
Authors: FREED S. CHARLES , GEORGE SHIRLEY ST. , ROSENMAN RAY H.
Published: June 2012

An elevation of potassium content of the aorta is found in renal hypertensive rats. Reduction of hypertension by potassium deprivation is followed by a proportional decrease in the aorta potassium content. Restoration of hypertension in such rats by cortisone administration is associated with a return of the aorta potassium content to the previous elevated levels. It is suggested that the potassium content of the arteries influences arterial tone and, by altering peripheral vascular resistance, may be a significant factor in blood pressure regulation.
Response of Subcutaneous Vessels to Venous Distention
Authors: WIEDEMAN MARY P.
Published: June 2012

Direct observations of circulation in small vessels of the bat wing indicated that increased resistance to arterial flow could be produced by venous distention without active vasoconstriction.
Observations on the Microcirculation in the Gingiva of Hamsters and Other Laboratory Animals
Authors: STAPLE P. H. , COPLEY A. L.
Published: June 2012

By using the teeth for immobilisation and employing incident light microscopy at magnifications up to 240x, entire capillary beds could be observed in the labial gingiva in small laboratory animals. In the mandibular incisor region, simple capillary loops, as found in the human gingiva and nail bed, were absent in all species examined except in some guinea pigs. In the hamster, where the topography of the gingival capillary bed was studied in greatest detail, blood flow was regulated by changes in caliber of arterioles; by opening and closing of exits from main capillary channels into networks apparently devoid of vasomotor activity; and by opening and closing of arteriovenous anastomoses. Under certain conditions, settling of blood cells and blood cell clumps to the lower side of gingival veins, together with gravitationally layered flow, was observed.
Effect of Hemorrhage on Hepatic Blood Flow Determined by Radioactive Colloidal Chromic Phosphate Removal
Authors: McC. SMYTHE CHEVES
Published: June 2012

In a group of 18 anesthetized dogs hepatic blood flow measured by the BSP removal technic of Bradley and the radioactive colloidal chromic phosphate disappearance method of Dobson gave comparable results of 38.7 and 38.3 ml./Kg./min. respectively. In response to acute hemorrhage of 25 ml./Kg., hepatic blood flow fell from 42.3 to 35.4 ml./Kg. A more severe hemorrhage of 33 ml./Kg. produced a more profound decrease of hepatic blood flow, from 43.4 to 20.8 ml./Kg./min.
The Electric Field Produced by an Eccentric Dipole in a Homogeneous Circular Conducting Lamina
Authors: BAYLEY ROBERT H.
Published: June 2012

In a manner essentially similar to that adopted by Helmholtz and particularized by F. N. Wilson and R. H. Bayley for the solution of the potential of the arbitrary dipole in the homogeneous spherical conductor, the corresponding solution is developed for an arbitrary dipole potential in and on the boundary of a homogeneous circular plane lamina. The formulas for the latter solution are simple when compared with those for the sphere, and should therefore prove useful in testing measuring circuits and lead methods before attacking clinical electrocardiographic problems. A table is computed for positions of the zero of potential on the boundary, using 15 equal increases of dipole eccentricity both for the circular plane lamina and for the sphere.
A Figure of Merit For Catheter Sampling Systems
Authors: SHERMAN H. , SCHLANT R. C. , KRAUS W. L. , MOORE C. B.
Published: June 2012

The distortion of indicator dilution curves by catheter sampling systems is predictable from theoretic considerations based on laminar flow. Over a wide range of catheter and flow parameters, deductions can be made regarding distortion, by the arterial system or by sampling catheters, of indicator dilution curves coming from an idealized pump. A figure of merit for the sampling system is given by the volume of the catheter divided by twice the flow rate. This number should be less than the time in which significant changes in indicator concentration occur, i.e., the interval between pump strokes, if significant distortion of the indicator dilution curve is to be avoided.
Circulation of Labeled Albumin Through the Aortic Wall of the Dog
Authors: DUNCAN LEROY E. , CORNFIELD JEROME , BUCK KATHERIN
Published: June 2012

Data are presented which support the concept that albumin enters the inner layer of the aortic wall by passage from the lumen of the aorta across the intimal endothelium. The rate of movement of albumin from serum into the aortic wall is much greater proximally where the aorta is wide than distally where it is narrow. Thus the rate correlates with the circumferential tension to which the aortic wall is subjected. The hypothesis is advanced that circumferential tension acts as a major determinant of transendothelial transfer of proteins into the aorta by widening the endothelial intercellular spaces through which the transfer occurs.
Effect of Potassium and "Toxic" Doses of Digitalis on the Myocardium
Authors: FISCH CHARLES , STEINMETZ EDWARD F. , FASOLA ALFRED F. , MARTZ B. L.
Published: June 2012

This study was designed to evaluate further the antagonism between digitalis and potassium. Potassium was given by intravenous infusion to six dogs (1) before digitalization, (2) after injection of "therapeutic" doses of digitoxin, and finally (3) after injection of "toxic" doses of the drug.
Effect of Age and Coronary Artery Disease on the Postural Adjustment of Peripheral Circulation
Authors: SIMONSON ERNST
Published: June 2012

Circulatory regulation tends to minimize gravitational effects of postural changes. The changes of the extracranial volume pulse, recorded by means of an impedance plethysmograph, in tilted head-up and head-down position, are significantly greater in older than in younger men, indicating impairment of circulatory postural regulation with age. Surprisingly enough, this impairment is partially compensated in coronary patients, possibly due to hyperactive carotid sinus reflexes.
Theoretical and Practical Requirements for the Valid Measurement by Indicator-Dilution of Regurgitant Flow Across Incompetent Valves
Authors: LACY WILLIAM W. , GOODSON WILLIAM H. , WHEELER WILLIAM G. , NEWMAN ELLIOT V.
Published: June 2012

A theory is presented for the measurement of regurgitant flow across an incompetent valve by injection of indicator distal to the valve and recording of time concentration curves proximal and distal to the valve. The conditions which must be met for valid measurements are examined and demonstrated by a functioning mechanical model of the heart. The method is valid regardless of the size of the residual volumes or degree of mixing with these volumes if a representative sample of the concentration of indicator in the blood moving across the valve in both directions is obtained.
Perfusion of a Strip of Mammalian Ventricle
Authors: DÉLEZE JEAN
Published: June 2012

A preparation of sheep's or calf's myocardium is described: the m. transversus cordis of the right ventricle. This lends itself to perfusion of its capillary bed as well as to the recording of membrane potentials from single fibers. When the Na concentration in the perfusate is reduced, the action potentials undergo changes that suggest that the "sodium hypothesis" is applicable to cardiac ventricle.
Physiologic and Anatomic Effects of Propylthiouracil on Normal and Hypertensive Rats
Authors: FREGLY M. J. , HOOD C. I.
Published: June 2012

The antithyroid drug propylthiouracil prevented or removed the hypertension associated with bilateral kidney encapsulation with latex envelopes. This effect did not appear to be the result of hypofunction of the adrenal glands. Propylthiouracil reduced growth rate in young rats and caused weight loss in adult rats. The latter effect appeared to be true tissue loss because water contents of heart, kidney, testes, liver, psoas, aorta and adrenal were unaffected. Administration of propylthiouracil for 7 to 19 weeks tended to reduce heart weight to body weight ratio as well as the ratio of kidney weight to body weight in both control and "encapsulated" rats. However, ratios of organ weight to body weight in the cases of thyroid, testes and eyes were larger than those of untreated control rats. In addition to its antihypertensive effect, propylthiouracil treatment of encapsulated rats also prevented the appearance of certain other manifestations of hypertension usually accompanying kidney encapsulation.
The Adrenal Gland and the Cardiovascular Changes in Acute Anoxic Anoxia in Dogs
Authors: BAUGH C. W. , CORNETT R. W. , HATCHER J. D.
Published: June 2012

The hyperkinetic circulatory state observed in intact anesthetized dogs at the end of a 15 minute period of breathing 6 per cent oxygen in nitrogen was absent in a similar series of dogs acutely adrenalectomized by the ligation technie. Blood removed from intact animals at the end of the anoxic period and infused into normal assay dogs produced a rise in cardiac output in the latter which was not observed with comparable infusions of normal blood or blood removed from adrenalectomized anoxic dogs. The transferable agent demonstrated by this study is considered responsible for the rise in cardiac output in the anoxic donor. It is suggested that this agent arises from the adrenal medulla.
Changes in Heart Rate During Levarterenol Infusion
Authors: FINNERTY FRANK A. , TUCKMAN JOHN , HAJJAR GEORGE C.
Published: June 2012

Studies in this laboratory have demonstrated varying responses in heart rate during levarterenol-induced hypertension. A decreased bradycrotic response did not seem to depend on the age of the patient, the control level of arterial pressure or the percentage increase in mean arterial pressure. The present study was designed to evaluate the factors which govern the changes in heart rate during levarterenol infusion.
Responses of Dog's Pad Vessels to Epinephrine Following Sympathectomy or Denervation
Authors: COOPER THEODORE , WILLMAN VALLEE L. , HERTZMAN ALRICK B.
Published: June 2012

Augmented reactivity of the skin vessels of the hind limbs of dogs to doses of l-epinephrine in the physiologic range could not be detected following conventional sympathectomy. Larger doses of epinephrine resulted in exaggerated reactions. Augmented reactivity of these vessels to physiologic doses of epinephrine was detectable if total cholinergic as well as adrenergic denervation of the limb was accomplished.