bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of ischemic zone size on nonischemic area function in the canine left ventricle
Authors: Lew W. Y.
Published: December 2017

The relationship between ischemic zone size and nonischemic area function was examined in seven anesthetized dogs. Regional ventricular function was measured with sonomicrometers implanted in the midwall of the anterior apex, posterior base, and posterior apex of the left ventricle. Ventricular volume was varied to three levels, corresponding to left ventricular end-diastolic pressures of 7, 12, and 19 mmHg. A small, moderate, and large area of anterior wall ischemia was produced with sequential occlusions of the distal, mid, and proximal left anterior descending coronary artery, respectively. Each occlusion was maintained for 15-30 min; then ventricular volume was varied to three levels, chosen so that end-diastolic segment lengths in the nonischemic areas were matched to their control (preischemia) values. With acute ischemia, paradoxical lengthening developed in the ischemic zone during isovolumic systole. This was accompanied by an increase in isovolumic shortening in the nonischemic areas. The amount of nonischemic area isovolumic shortening increased with increasing ischemic zone size, suggesting that more nonischemic area shortening was expended in paradoxically stretching the ischemic zone. With moderate and large areas of ischemia, the amount of "wasted" isovolumic shortening by nonischemic areas was greater at low than at high ventricular volumes. It is concluded that the ischemic zone imposes a mechanical disadvantage on nonischemic areas in direct relation to ischemic zone size and is inversely related to the ventricular volume.
Myocardial amino acid transport by canine sarcolemma vesicles
Authors: Young L. H. , Zaret B. L. , Barrett E. J.
Published: December 2017

The transport of L-alanine and L-leucine into membrane vesicles isolated from mature canine ventricular myocardium was studied. Transport was assessed in purified sarcolemma and in vesicles differentially enriched either for sarcolemma or sarcoplasmic reticulum to further localize these transport systems. An imposed inward gradient of a NaNO3 stimulated uptake of L-alanine but not L-leucine by these vesicles. Amino acid uptake by these vesicles occurred into an osmotically active space. The stimulatory effect of Na+ on alanine transport was most striking in the purified sarcolemma vesicles, where Na+-stimulated alanine flux was 45 +/- 14 pmol X mg-1 X min-1. Furthermore, Na+-dependent alanine transport activity appeared to copurify with Na+-K+-ATPase activity, which served as a marker for sarcolemma membrane when these activities were compared in the three different membrane preparations. Leucine transport by sarcolemma was not altered by an imposed Na+ gradient. However, leucine uptake was a saturable function of extravesicular leucine and was inhibited by valine. In contrast, in sarcoplasmic reticulum membrane vesicles leucine uptake increased proportionately with increasing media leucine and was unaffected by valine. Our results demonstrate the feasibility of directly studying the transport of naturally occurring amino acids in membrane vesicles from mammalian heart, and the presence of Na+-dependent alanine transport system and a Na+-independent leucine transporter in the sarcolemma but not in sarcoplasmic reticulum of canine ventricular myocardium.
Cardiac and arterial baroreceptor influences in release of vasopressin and renin during hemorrhage
Authors: Quail A. W. , Woods R. L. , Korner P. I.
Published: December 2017

We studied the role of arterial and cardiac baroreceptors on mean arterial pressure (MAP) and release of arginine vasopressin (AVP) and plasma renin activity (PRA) during hemorrhage in conscious rabbits. Each rabbit was bled at 2% of its blood volume (BV) per minute until 35% had been removed, after which the blood was reinfused. Each rabbit was studied on three occasions, 7 days apart, and in each experiment, BV-MAP and BV-hormone response curves were constructed. The response to hemorrhage was examined when the input from arterial and cardiac baroreceptors were both intact; arterial baroreceptors only were intact (cardiac receptors were blocked with intrapericardial procaine); cardiac receptors only were intact (after sinoaortic denervation); neither receptor was intact. Resting AVP and PRA levels were unaffected by the various deafferentation procedures. AVP steeply increased only after more than 25% BV had been removed; this response was entirely mediated by cardiac baroreceptors. Increases in PRA occurred at BV loss greater than 15% and were largely independent of baroreceptor input. Maintenance of MAP during hemorrhage was mostly due to drive from the arterial baroreceptors. Thus AVP secretion during hemorrhage contributes little to the maintenance of MAP, and the hypovolemic stimulus to AVP release comes entirely from the cardiac baroreceptors.
Contractility-dependent curvilinearity of end-systolic pressure-volume relations
Authors: Burkhoff D. , Sugiura S. , Yue D. T. , Sagawa K.
Published: December 2017

The shape of the end-systolic tension-length relationship (ESTLR) changes when contractile state is changed, whereas the end-systolic pressure-volume relationship (ESPVR) remains linear despite changes in contractility. To investigate this disparity, the ESPVR was determined with contractility altered extensively by dobutamine, BAY K 8644, nifedipine, lowering coronary blood flow, and the introduction of extrasystolic and postextrasystolic stimulations. The ESPVRs were fitted by nonlinear regression analysis to the parabolic equation Pes = aVes2 + bVes + c, where Pes is end-systolic pressure, Ves is end-systolic volume, and a, b, and c are parameters. There was a negative, statistically significant correlation between a, which serves as a shape index of the ESPVR, and E'max, the slope of the ESPVR in a low volume range. When E'max was large a was negative, indicating increasing concavity of the ESPVR to the volume axis at high contractility. When E'max was small a was positive, indicating convexity of the ESPVRs to the volume axis at low contractility. Within the average range of E'max between 3.4 and 7.8 mmHg/ml, however, the parabolic fit to the data was not statistically better than a linear fit over the range of volumes testable in the isolated heart. We conclude that the shape of the ESPVR measured in the isolated canine heart changes with contractile state. In accordance with previous interpretations of shape changes in the muscle ESTLR, these results are consistent with the existence of length-dependent activation of cardiac muscle in the intact heart.
Whole body structural vascular adaptation to prolonged hypoxia in chick embryos
Authors: Adair T. H. , Guyton A. C. , Montani J. P. , Lindsay H. L. , Stanek K. A.
Published: December 2017

We studied the role of hypoxia in the development of the blood vascular system using functional measurements of whole body and hindlimb structural vascular resistance in the chick embryo. The method is based on a newly developed whole body perfusion technique in which the maximally dilated blood vasculature of 14- to 15-day chick embryos is perfused through the extraembryonic blood vessels. Embryos were grown in 12% oxygen (Po2 65 mmHg, n = 18) or 16% oxygen (Po2 96 mmHg, n = 19) for the last 7 days of incubation and were compared with weight-matched (n = 17) and age-matched (n = 18) normoxic control groups (Po2 134 mmHg). Pressure-flow curves were generated for all embryos by increasing and decreasing the aortic pressure along 1-mmHg steps over a pressure range of 0-6 mmHg. Venous pressure was held at 0 mmHg by allowing the perfusate to flow freely from severed extraembryonic veins. The hydraulic resistance of the maximally dilated vascular bed, called the "structural vascular resistance," was decreased in a dose-related manner in the hypoxic groups to greater than 50% of control in the whole body and hindlimbs of the 12% oxygen group. The vessels of the 12% oxygen group were able to carry two and three times as much flow to the whole body and hindlimb tissues, respectively, as compared with the weight-matched normoxic control group. Therefore, the results support the hypothesis that prolonged exposure to hypoxia causes the blood vascular system to adapt its structure to allow greater amounts of blood to flow to the tissues at any given perfusion pressure gradient.
Beat-to-beat estimation of peripheral resistance and arterial compliance during pressure transients
Authors: Toorop G. P. , Westerhof N. , Elzinga G.
Published: December 2017

We have used a computer-based parameter estimation method to obtain peripheral resistance, total arterial compliance, and characteristic resistance from the measurement of aortic pressure and flow in the open-thorax cat, assuming the three-element windkessel as a model of the systemic arterial tree. The method can be applied on a beat-to-beat basis in the steady state and in transients. We have validated this method by analyzing nonsteady-state data obtained from an electrical analog with fixed values of the resistances and compliance and by showing that the values obtained by this procedure were within 5% of the fixed values of the circuit. Changes in total peripheral resistance and arterial compliance were studied before, during, and after acute heart rate changes in five open-thorax cats with blocked autonomous nervous system. As expected, the peripheral resistance, estimated during the heart rate transient [3.93 +/- 0.94 (SE) kPa X ml-1 X s] was the same as before the transient (3.53 +/- 0.83 kPa X ml-1 X s); total arterial compliances were also identical (0.28 +/- 0.04 vs. 0.27 +/- 0.03 ml/kPa). In six cats without nervous blockade we obtained similar results. Calculation of peripheral resistance during transients from the mean pressure-to-mean flow ratio, i.e., without correction for arterial compliance, suggested changes in resistance values of less than or equal to 57%, which shows that correction is necessary. The findings indicate that peripheral resistance and total arterial compliance can be estimated in vivo on a beat-to-beat basis, even during hemodynamic transients.
Relation between oxygen consumption and pressure-volume area of in situ dog heart
Authors: Nozawa T. , Yasumura Y. , Futaki S. , Tanaka N. , Igarashi Y. , Goto Y. , Suga H.
Published: December 2017

Page H31: T. Nozawa, Y. Yasumura, S. Futaki, N. Tanaka, Y. Igarashi, Y. Goto, and H. Suga. “Relation between oxygen consumption and pressure-volume area of in situ dog heart.” Page H37: Fig. 6: Although the last sentence of the legend states “Solid lines are linear regression lines, and inner and outer pairs of dashed curves around them are 95% confidence limits of regression lines and data points, respectively,” these dashed lines show one standard deviation of both the slope of the regression line and the sampled data from the regression line. The authors forgot to multiply these standard deviation values by t value (2.069 for degrees of freedom = 23) for P le 0.05 in the computer software to obtain the 95% confidence limits. The other statistical results in Fig. 6 are correct.
Postnatal changes in critical cardiac output and oxygen transport in conscious lambs
Authors: Fahey J. T. , Lister G.
Published: December 2017

We lowered cardiac output progressively in a controlled, stepwise fashion in conscious, unsedated lambs to determine the critical cardiac output or systemic oxygen delivery (the level at which oxygen consumption decreased abruptly). With the use of incremental inflation of a balloon-tipped catheter placed in the right atrium to lower cardiac output, we examined the response of oxygen consumption, systemic oxygen transport, fractional oxygen extraction, arterial lactate, and blood pressure. We studied lambs at 2 (n = 5), 4 (n = 5), and 8 wk (n = 6) of age and found that the 4-wk-old lambs reached critical values of cardiac output and systemic oxygen transport with the smallest proportional decreases from base-line values. Therefore, the 4-wk-old lambs were the least tolerant of acute decreases in cardiac output. We also found that fractional oxygen extraction was able to increase even after critical systemic oxygen transport was achieved. Furthermore, we found at every age that lactic acid accumulation began when the critical level of cardiac output was reached.
Substrate use in ischemic and reperfused canine myocardium: quantitative considerations
Authors: Myears D. W. , Sobel B. E. , Bergmann S. R.
Published: December 2017

The patterns of use of substrate in reperfused myocardium are not yet well elucidated, and their delineation is essential for adequate interpretation of results of analyses performed after positron emission tomography with labeled substrates to differentiate normal from abnormal heart muscle. Accordingly, in open-chest, anesthetized dogs we measured glucose and fatty acid utilization in normal, ischemic, and reperfused myocardium and assessed the contributions of metabolism of each substrate to overall oxidative metabolism. Intracoronary [3H]glucose and [14C]palmitate were administered in five control dogs, eight dogs subjected to 1 h of coronary occlusion, and nine dogs subjected to reperfusion after 1 h of ischemia. Regional coronary venous blood samples were assayed sequentially. In reperfused myocardium, utilization of glucose (463 +/- 88 nmol X g-1 X min-1) was 103% greater than that in ischemic and 273% greater than in normal myocardium (P less than 0.05 for each). Utilization of fatty acid during reperfusion (55 +/- 10 nmol X g-1 X min-1), although greater than that in ischemic myocardium, was significantly less than that in normal myocardium (48% of control, P less than 0.05) despite restoration of flow to 80% of control values. Although glucose constituted 70% of the substrate oxidized in ischemic myocardium, its contribution to overall oxidative metabolism in reperfused myocardium was only 25%. In contrast, despite diminished net uptake of fatty acid, oxidation of fatty acid accounted for 63% of total oxygen consumption in reperfused myocardium. These studies indicate that canine myocardium reperfused after 1 h of ischemia exhibits enhanced uptake of glucose and impaired utilization of palmitate.(ABSTRACT TRUNCATED AT 250 WORDS)A
Quantitative analysis of arteriolar network architecture in cat sartorius muscle
Authors: Koller A. , Dawant B. , Liu A. , Popel A. S. , Johnson P. C.
Published: December 2017

The geometry of the arteriolar network is one of the major determinants of blood flow distribution within a tissue. The purpose of this study was to describe the distribution of geometrical variables (lengths, diameters) as well as the pattern of branching in the nonarcading portion of the arteriolar network in skeletal muscle. The exteriorized cat sartorius muscle was used as the experimental model. The intravascular fluorescence of fluorescein isothiocyanate (FITC)-labeled Dextran 150 was observed with a low-light-level video camera, and the vascular networks were mapped. Arteriolar lengths and diameters were measured, and vessel position in the network was characterized by Strahler's method of ordering, in which the first-order arterioles give rise to most of the capillaries. Typically, the nonarcading, terminal networks contain three or four arteriolar orders. The sequences of the number of vessels, mean diameter, and mean length for each order are accurately described by geometric progressions (Horton's law). The distribution of diameters within each order was rather narrow: typically two-thirds of the vessels fell within 20% of the mean value. The spread was reduced by half when vessels within a single network were considered. During vasodilation to a standard stimulus the relative dispersion of diameters increased modestly. The distribution of vessel lengths was broader than for diameters. Two-thirds of vessels of a single order fell within 50–75% of the mean. The spread was less within individual networks. The variability of vessel geometry and branching patterns was substantially less within a single network than for a population drawn from a group of networks.
Role of adenosine in regulation of cerebral blood flow: effects of theophylline during normoxia and hypoxia
Authors: Morii S. , Ngai A. C. , Ko K. R. , Winn H. R.
Published: December 2017

We studied the effects of the methylxanthine theophylline, an adenosine receptor blocker, on cerebral circulation. Cerebral blood flow (CBF) was measured by the retroglenoid outflow and microsphere techniques, and pial circulation changes were observed through a closed cranial window. Intraperitoneal administration of theophylline in normoxic animals resulted in a biphasic response of pial vessels and CBF. At low concentrations (0.05 mumol/g) of theophylline, pial vessel diameter and CBF decreased, whereas vasodilatation and hyperemia were observed at higher levels. After intraperitoneal administration of either 0.05 or 0.2 mumol/g, hypoxic hyperemia was attenuated both during short (c. 30 s) and sustained (c. 2–3 min) hypoxia, as was hypoxic pial arteriolar vasodilatation. These actions of theophylline appear to be due to adenosine receptor blockade, since micromolar concentrations were achieved in cerebrospinal fluid (CSF), and no increases in adenosine 3',5'-cyclic monophosphate concentrations in brain were noted. Moreover, theophylline (either intraperitoneal or topical) blocked pial vasodilatation caused by topically applied adenosine, but had little effect on hypercarbic hyperemia or pial vasodilatation induced by topically applied acetylcholine. The results of these studies suggest that adenosine is involved in the maintenance of resting cerebral vascular tone and has a paramount role in the regulation of CBF during hypoxia.
Increased vascular resistance during complement-activated plasma infusion in swine
Authors: Swenson L. J. , Pantely G. A. , Anselone C. G. , Bristow J. D.
Published: December 2017

To investigate the acute effects of complement activation on blood flow, we infused complement-activated plasma into the femoral artery of the isolated hindlimb of 19 anesthetized swine. Femoral artery blood flow decreased abruptly, was lowest at 1 min of the infusion, and thereafter slowly increased despite continued infusion. There was no significant change in femoral artery pressure or femoral vein pressure, confirming an acute increase in vascular resistance. Control infusion of heat-decomplemented-activated plasma caused no change in pressure or flow. Slope of the femoral artery pressure-flow relationship during maximal vasodilation with adenosine was significantly lower after infusion of complement-activated plasma, confirming a persistent increase in vascular resistance. Neither the acute nor the persistent increase in vascular resistance was prevented by alpha-adrenergic blockade with phentolamine or granulocytopenia produced by cyclophosphamide. We conclude that complement-activated plasma infusion in the femoral circulation causes an abrupt increase in vascular resistance that persists during pharmacologically maximal vasodilation, is not due to alpha-mediated vasoconstriction, and is not altered by severe granulocytopenia.
Biaxial mechanical properties of human pericardium and canine comparisons
Authors: Lee M. C. , Fung Y. C. , Shabetai R. , LeWinter M. M.
Published: December 2017

The two-dimensional mechanical properties of human pericardium from seven males undergoing coronary artery bypass surgery were studied. A 25-mm square piece of parietal pericardium overlying the right ventricle was excised. An approximately 8-mm square target was marked at the center, and its dimension was measured electrooptically. When immersed in physiological saline at 37 degrees C, the specimen was subjected to biaxial isotropic loading. Large deformations developed in the beginning of the loading; the pericardium became increasingly stiffer when load was increased, and then became almost inextensible. As in canine pericardium [Lee et al., Am. J. Physiol. 249 (Heart Circ. Physiol. 18): H222-H230, 1985], hysteresis was present and tension-stretch relationship was insensitive to loading frequency during cyclic loading, relaxation of tension was substantial, and creep was insignificant. Unlike canine specimens, however, human pericardium was nearly isotropic and almost three times as thick [mean 0.55 +/- 0.02 mm (SD)]. The human tension-area relation for isotropic loading could be described by an exponential function and was found to shift significantly to the left of the canine. Therefore, human pericardium is less extensible than canine.
Brachial arterial changes in response to wrist occlusion in normotensive and hypertensive men
Authors: Levenson J. , Simon A. , Pithois-Merli I.
Published: December 2017

Diameter, blood velocity, and flow of the brachial artery and vascular resistance of the brachial circulation were evaluated with a pulsed Doppler velocimeter before and after wrist occlusion in 8 younger and 8 older normotensive subjects and in 11 younger and 11 older hypertensive patients. Before occlusion, no differences existed between younger and older normotensives. However, in hypertensives, systolic peak velocity was higher in younger than in older hypertensives (P less than 0.001) and correlated to age in the overall patients (r = -0.57, P less than 0.01). Occlusion decreased velocity and flow and increased vascular resistance in all groups, but the change in resistance was not correlated with the base-line resistance. During occlusion, no differences existed between younger and older normotensives. However, in hypertensives mean and systolic peak velocity was higher (P less than 0.01), and vascular resistance was lower (P less than 0.01) in younger than in older patients. In hypertensive patients, during occlusion mean and systolic peak velocity were negatively correlated to age (r = -0.72, P less than 0.001; r = -0.59, P less than 0.01), and vascular resistance was positively related to age (r = +0.66, P less than 0.001). Thus wrist occlusion modified the brachial circulation in normotensive and hypertensive populations but revealed age-related differences only in hypertensive patients, suggesting a combined effect of age and hypertension on the muscle vascular bed.
Protective effect of transient calcium reduction against reperfusion-induced arrhythmias in rat hearts
Authors: Tosaki A. , Hearse D. J.
Published: December 2017

By using the isolated rat heart with regional ischemia and a perfusate Ca2+ of 2.4 mM, we have observed a bell-shaped relationship between the incidence of reperfusion-induced ventricular fibrillation (VF) and the duration of preceding ischemia. With 5, 10, 20, 30, and 40 min of ischemia, 8, 83, 58, 25, and 8% of the hearts (n = 12 per group) exhibited irreversible VF. In additional studies (10 min ischemia) perfusate Ca2+ was reduced (to 0.1, 0.4, 0.8, 1.2, 1.6, and 2.0 mM) for 1 min before coronary occlusion (to trap low Ca2+ in the ischemic zone) and for 1 min before and throughout reperfusion. VF fell in a dose-dependent manner from its control incidence of 83% (2.4 mM Ca2+) to 17 (P less than 0.01), 25 (P less than 0.01), 41, 58, 91, and 83%, respectively. In further studies Ca2+ was reduced to 0.4 mM just before ischemia and also just before and during reperfusion, and the ischemic time was varied (5, 10, 20, 30, or 40 min), VF was reduced from its time-matched control (2.4 mM Ca2+) values of 8, 83, 58, 25, and 8% to 0, 25 (P less than 0.01), 8 (P less than 0.05), 0, and 0%, respectively. In a final series of experiments, Ca2+ reduction (to 0.4 mM) was carried out only during reperfusion (1 min before and throughout reperfusion). When time-vulnerability curves were constructed some protection was observed after 20 min of ischemia (VF fell from its control incidence of 58 to 8%). We conclude that extracellular Ca2+ concentration can influence vulnerability to reperfusion-induced arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)
Post-reextension force decay of relaxing cardiac muscle
Authors: Sys S. U. , Paulus W. J. , Claes V. A. , Brutsaert D. L.
Published: December 2017

Residual active cardiac muscle force during ventricular filling causes deviations of the pressure-volume and pressure-segment length relations from passive left ventricular compliance curves. A possible interaction at the myocardial level between muscle reextension and subsequent active force decay has not yet been investigated. We therefore studied the relation between isolated cat papillary muscle reextension, load during reextension, and isometric force decay after isotonic reextension. Both timing and extent of the isotonic muscle reextension phase were altered while load during reextension was lowered, subsequent residual isometric force was decreased. The extent of reextension or the final muscle length did not alter residual active isometric force after isotonic reextension at an identical load. Moreover, irrespective of the loading history of the shortening phase of the contraction, equal loads during reextension resulted in superimposable subsequent isometric force decay traces. From these results it therefore appears that residual isometric force after isotonic reextension is determined by the load during reextension. Extrapolation of these results to the filling ventricle implies the existence of a dynamic interaction between instantaneous extent of filling, wall stress, and residual force development.
Time course of aerobic recovery after contraction of rabbit papillary muscle
Authors: Mast F. , Elzinga G.
Published: December 2017

The time course of oxygen uptake after isometric twitch contractions of isolated rabbit papillary muscles was determined at 20 degrees C by continuous polarographic measurement of the partial pressure of oxygen in a 219-microliters glass chamber in which the fluid circulated rapidly. The response time of the oxygen-measuring system was characterized by a delay of 1.1 s and a time constant of 2.1 s after that delay. Depending on the stimulation frequency (0.125–1.0 Hz) the total amount of oxygen uptake for 120 twitches varied from 5.3 to 32.7 nmol/mg dry wt, and the steady-state oxygen consumption rate varied from 0.4 to 8.5 nmol X min-1 X mg dry wt-1. On the basis of a diffusion model we eliminated the effect of oxygen storage on the measured time course of oxygen consumption to determine the mitochondrial kinetics. We found a time constant of an average 19–22 s of mitochondrial off kinetics. By use of this time constant for the change in oxygen consumption rate after contraction, it can be estimated that 9–10% of the oxygen required to restore ATP levels is already taken up by the mitochondria during the twitch.
Postpacing tachycardia: autonomic involvement
Authors: Loeb J. M. , deTarnowsky J. M. , Warner M. R. , Whitson C. C.
Published: December 2017

The cessation of pacing from the sinus node region is followed by a transient sinus tachycardia or postpacing tachycardia (PPT). We sought to characterize autonomic involvement in PPT. We used alpha-chloralose-anesthetized dogs and recorded electrocardiograms, blood pressure, and electrograms from the sinus node, right atrium, right ventricle, and His bundle. Both vagi and both stellate ganglia were transected. PPT developed immediately after either linear or stepped heart rate changes. PPT followed pacing from the rostral but not the caudal region of the sulcus terminalis. Independent manipulation of absolute level of heart rate (+33, +66, and +100 beats/min above control) and duration of atrial pacing (10, 20, and 30 s) revealed that PPT is dependent predominantly on the duration of pacing and less on level of heart rate. During pacing in the control state, a 1:1 atrial capture was maintained. After atropine administration (0.2 mg/kg iv), PPT increased significantly in magnitude, time to peak PPT was shortened significantly, and loss of 1:1 atrial capture during pacing was evident at pacing rates of from 10 to 60 beats above control. In contrast, propranolol significantly attenuated PPT. We conclude that acetylcholine, released during pacing from the sinus node region, suppresses inherent sinus node acceleration induced by the concurrent release of intramural catecholamines. During pacing, acetylcholine release is essential for the maintenance of 1:1 atrial capture and significantly modulates both the latency and magnitude of PPT.
Chronic pressure overload hypertrophy decreases direct ventricular interaction
Authors: Slinker B. K. , Chagas A. C. , Glantz S. A.
Published: December 2017

We studied the relative roles of direct (via the interventricular septum) and series (via the pulmonary circulation) ventricular interaction in hearts with concentric left ventricular hypertrophy by using statistical models to analyze the transient responses in right and left ventricular pressures and dimensions to occlusions of the venae cava and pulmonary artery in five open-chest anesthetized dogs. The left ventricles of these dogs had moderate concentric hypertrophy (31% increase in mass) induced by 3 mo of renovascular hypertension [peak left ventricular pressure = 160 +/- 13 (SD) mmHg]. At end diastole we found that direct interaction was only about one-tenth as important as series interaction in determining left ventricular size with the pericardium around the heart. At end systole we found that direct interaction was about one-fifth as important as the end-systolic pressure-volume relationship in determining left ventricular size. Removing the pericardium decreased the importance of direct interaction. Direct interaction is less important in these hearts than in normal hearts, probably because the septum is thicker and, hence, less distensible. This change in the relative importance of direct ventricular interaction with hypertrophy complicates comparison of pressure-volume relationships between normal and hypertrophied hearts.
Dopaminergic stimulation of cAMP accumulation in cultured rat mesangial cells
Authors: Shultz P. J. , Sedor J. R. , Abboud H. E.
Published: December 2017

Dopamine (DA) alters renal hemodynamics, and DA receptors have been demonstrated in isolated glomeruli. To determine the glomerular cell type bearing DA receptors, we studied the effect of dopaminergic agonists and antagonists on adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in rat glomerular mesangial and epithelial cells in culture. DA caused a marked dose- and time-dependent increase in cAMP accumulation in mesangial but not epithelial cells. The stimulatory effect of DA was abolished by the DA antagonists haloperidol, trifluoperazine, and cis-thiothixene but not by beta- or alpha-adrenergic or histamine antagonists. Similar to the effects of DA, two dopamine type I receptor agonists, fenoldopam and SKF 38393, markedly stimulated cAMP accumulation in the mesangial cells. Moreover, the effects of DA were blocked by Sch 23390, a specific DA1 receptor antagonist, but not domperidone, a specific DA2 antagonist. These results show that DA regulates cAMP accumulation in mesangial cells via DA1-type receptors.
Coronary vasoconstriction mediated by alpha 1- and alpha 2-adrenoceptors in conscious dogs
Authors: Woodman O. L. , Vatner S. F.
Published: December 2017

Coronary vasoconstriction was examined in response to the selective stimulation of alpha 1- and alpha 2-adrenoceptors in chronically instrumented conscious dogs. Norepinephrine (NE, 0.05 and 0.1 micrograms X kg-1 X min-1), a mixed alpha 1- to alpha 2-adrenoceptor agonist, phenylephrine (PE, 0.5 and 1.0 micrograms X kg-1 X min-1), a preferential alpha 1-adrenoceptor agonist, and B-HT 920 (1.0 micrograms X kg-1 X min-1), a preferential alpha 2-adrenoceptor agonist, were infused intravenously after ganglionic (hexamethonium, 30 mg/kg iv), beta-adrenoceptor (propranolol, 1.0 mg/kg iv), and muscarinic receptor (atropine methylbromide, 0.1 mg/kg iv) antagonism. Equipressor doses of the alpha-adrenoceptor agonists caused similar increases in calculated late diastolic coronary resistance (NE, 0.57 +/- 0.10 mmHg X ml-1 X min; PE, 0.61 +/- 0.13 mmHg X ml-1 X min; B-HT 920, 0.64 +/- 0.09 mmHg X ml-1 X min). Mechanically increasing aortic root pressure to levels similar to those observed in response to alpha-adrenoceptor stimulation did not increase coronary resistance. Preferential antagonism of alpha 1-adrenoceptors with prazosin (1 mg/kg iv) abolished the vasoconstrictor response to PE but had a lesser effect on the response to B-HT 920. Antagonism of alpha 2-adrenoceptors with rauwolscine (alpha-yohimbine, 0.1 mg/kg iv) abolished the vasoconstrictor response to B-HT 920 but had a lesser effect on the response to PE. The response to NE was reduced to a similar degree by either alpha 1- or alpha 2-adrenoceptor antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)
Atrioventricular responses of canine heart following chronic unilateral vagotomy
Authors: Priola D. V. , Anagnostelis C. , Sanchez-Wilson C. , Blomquist T. M.
Published: December 2017

The intrinsic cardiac nerves (ICN) have been shown to develop supersensitivity to nicotine (NIC) following complete extrinsic cardiac denervation. The present experiments were performed to delineate the pattern of ICN distribution in the heart by examining the pattern of NIC supersensitivity after unilateral vagotomy (VGX). Thirty-eight dogs were placed on cardiopulmonary bypass and inotropy evaluated by means of isovolumic pressures from fluid-filled balloons placed in the atria and ventricles. The animals were divided into three groups: group I, sham-operated controls; group II, animals studied 1–2 wk after VGX; and group III, animals studied 8–12 wk after VGX. Chronotropic and inotropic responses were evaluated in terms of NIC and acetylcholine (ACh) dose-response curves as well as frequency-response curves to stimulation of the intact vagus nerve (0.5–30 Hz). No change in NIC sensitivity was observed in group II, and vagal frequency-response curves were identical to group I. In group III dogs, both the right atrium and right ventricle showed significant increases in NIC sensitivity after left vagotomy. All group III animals showed right-shifted frequency-response curves. We conclude that nicotinic supersensitivity of the ICN and inotropic unresponsiveness to vagal stimulation occur but are slow in developing (70–130 days); and preganglionic sprouting does not appear to play a functional role in the adjustment of cardiac control mechanisms to unilateral vagotomy.
Length-dependent sensitivity of vascular smooth muscle in normotensive and hypertensive animals
Authors: Coskinas E. , Price J. M.
Published: December 2017

Ring segments were obtained from the aorta of spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar (WST) rats and from the anterior tibial artery of normotensive and hypertensive dogs. Norepinephrine dose-response curves were generated at lengths relative to that for maximum force (Lmax) and at a specific preload (in grams). The doses of stimulus necessary to elicit 10 and 50% maximum force of contraction (ED10 and ED50) are greater at lengths less than Lmax than at Lmax for all groups. When SHR rings are compared with WKY or WST rings, ED10 or ED50 is the same at either length. The same result was found in comparing normal and hypertensive dogs. ED10 and ED50 from hypertensive groups were the same as their respective control groups when compared at the same preload. We conclude that sensitivity of the rat aorta and dog anterior tibial artery to norepinephrine depends on muscle length, this relationship is not altered in hypertension, and the conclusion on sensitivity in hypertension is the same for excised rings compared at the same length or at the same preload. Contractility (active stress) was lower (rats) or the same (dogs) but thickness was greater in the hypertensive groups than in their controls. The results show that a change in the vessel wall that can cause increased flow resistance and pressure is not in sensitivity or contractility but in wall thickness. Apparent differences in sensitivity from normal and hypertensive animals can be explained by an unchanged length-dependent sensitivity. The results also show that differences in body weight will affect a comparison of wall tension but not of sensitivity.
Quantitative comparison of canine right and left ventricular isovolumic pressure waves
Authors: Burkhoff D. , Kronenberg M. W. , Yue D. T. , Maughan W. L. , Hunter W. C. , Sagawa K.
Published: December 2017

The mechanical properties of the right and left ventricles (RV and LV) have previously been studied separately. However, because of differences in RV and LV architecture, geometry, and muscle mass, it is not obvious how the properties of the two chambers would relate to each other. This study compared the time courses of RV and LV isovolumic pressure waves (LVP, RVP, respectively) measured simultaneously in the same heart. We compared RVP and LVP in each of five isolated, supported canine hearts after pentobarbital anesthesia. RV and LV volumes were varied independently so that on various beats peak LVP exceeded, equaled, or was less than peak RVP. There was a delay of approximately 35 ms between the onset of LV and RV pressure waves with atrial pacing, but only 5 ms with ventricular pacing. LVP and RVP were measured and digitized at a sampling rate of 200 Hz. Pressure waves were offset and rescaled by their respective amplitudes so that for each beat the pressure wave had a minimum value of 0% at end diastole and a maximum value of 100% at end systole. RVP was then shifted in time so that its upstroke was synchronous with that of the LVP at the point of 50% of maximal developed pressure. The rescaled, time-shifted RVP was plotted as a function of the rescaled LVP for each point of the cardiac cycle, and the relation between the two was quantified by their root mean square difference (Drms). Drms averaged 2.3 +/- 1.5% (SD) for the first half of contraction, 1.5 +/- 0.4% for the second half of contraction, and 4.6 +/- 1.6% during relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood viscosity in small tubes: effect of shear rate, aggregation, and sedimentation
Authors: Reinke W. , Gaehtgens P. , Johnson P. C.
Published: December 2017

Apparent viscosity was determined in vertical glass tubes (ID 30.2-132.3 microns) with suspensions of human red cells in A) serum, B) saline containing 0.5 g/100 ml albumin, C) plasma, and D) plasma containing Dextran 250 at a feed hematocrit of 0.45. Pressure-flow relationships were obtained in a range of pseudo-shear rates (mu) between 0.15 and 250 s-1. Relative viscosities in the nonaggregating suspensions (A and B) were found to increase monotonically with decreasing mu. The Fahraeus-Lindqvist effect was present in the entire range of mu. In the two aggregating suspensions (C and D), viscosities increased initially in larger but not small tubes with declining mu and fell in all tubes at some characteristic mu (usually below 10 s-1). Viscosity reduction was greater in the larger tubes and in suspensions with greater aggregation tendency. With suspension D, the Fahraeus-Lindqvist effect was eliminated in the lowermost shear-rate range. The cell-free marginal zone increased in width (to a maximum of approximately 40% of tube radius) as viscosity declined. Measurements of viscosity and cell-free marginal zone were also performed with suspension C in tubes mounted in horizontal position. In contrast to vertical tubes, a monotonic increase in viscosity was found with decreasing mu, associated with cell sedimentation and development of a cell-free layer only in the upper portion of the tubes.
Hypoxia, bradykinin, and prostaglandins stimulate ischemically sensitive visceral afferents
Authors: Longhurst J. C. , Dittman L. E.
Published: December 2017

Ischemia of abdominal visceral organs is known to reflexly stimulate the cardiovascular system. The purpose of this study was to determine which of several potential chemical stimuli present during ischemia either directly stimulate or sensitize these afferents to respond to ischemia. Impulse activity was recorded in the right splanchnic nerve of anesthetized cats. First, we determined whether the afferents were ischemically sensitive by subjecting them to 2-6 min of regional ischemia through occlusion of the descending thoracic aorta. We then examined the afferents' response to systemic hypoxia by decreasing the inspired O2 and arterial injection of bradykinin or the prostaglandins (PG) E2, PGF2 alpha, or prostacyclin (PGI2). Sixty-one percent of the rapidly adapting A fibers and 47% of the C fibers were stimulated by ischemia, and of these, 78% of the A fibers and 44% of the C fibers tested were stimulated by hypoxia. The latency of response to hypoxia (60 +/- 12 s) was significantly longer than the chemoreceptor-induced pressor response (45 +/- 11 s). Each afferent stimulated by ischemia and/or hypoxia innervated a receptive field in the pylorus, intestine, porta hepatis, gallbladder or biliary tract, pancreas, or mesentery. Ninety percent of the ischemically sensitive A fibers and 80% of the ischemically sensitive C fibers responded to bradykinin, whereas 40% of the A fibers and 62% of the C fibers responded to PGE2, PGF2 alpha, or PGI2. Several endings responded to ischemia or hypoxia only after bradykinin or PGI2 had been injected. Thus approximately 50% of slowly adapting A and C fiber endings in abdominal visceral organs respond, or can be sensitized by bradykinin or PGI2 to respond, to ischemia and/or hypoxia. However, they are not as sensitive to hypoxia as carotid and aortic body chemoreceptors, since they respond well after the chemoreceptor-induced pressor response.
Tachycardia of carotid chemoreceptors originates in apneic asphyxia in dogs
Authors: Gupta P. D. , Singh M.
Published: December 2017

Using various anesthetics, we investigated the heart rate changes resulting from apneic asphyxia in paralyzed artificially ventilated dogs with 1) low control heart rate (LCHR) and 2) high control heart rate (HCHR). We observed that apneic asphyxia produced by stopping the ventilation pump for 1 min evoked tachycardia in dogs with LCHR and bradycardia in dogs with HCHR. In dogs breathing 100% O2 in the preapneic period, the tachycardia response was almost wholly abolished, whereas the bradycardia response was attenuated. Intracarotid injection of sodium cyanide induced a tachycardia response in dogs with LCHR and a bradycardia response in dogs with HCHR. The results suggest that 1) apneic asphyxia evokes tachycardia or bradycardia response depending on whether the resting cardiac vagal tone is high or low, respectively, and 2) both types of heart rate responses are in part due to stimulation of carotid chemoreceptors.
Little carbon dioxide diffusional shunting in coronary circulation
Authors: Katz S. A. , Feigl E. O.
Published: December 2017

The magnitude of CO2 countercurrent diffusional trapping (net diffusion from coronary venous to coronary arterial vessels) in the myocardium was determined. The left main coronary artery was pump perfused with a modified Gregg cannula in open-chest, heart-blocked, anesthetized dogs. Coronary venous PCO2, pH, and PO2 were simultaneously measured with a rapidly responding continuous electrode-cuvette system. Coronary venous CO2 concentration was calculated from the electrode outputs and a corresponding hemoglobin determination. After a step change in coronary flow, the amount of CO2 washed out or retained by the perfused myocardium was determined from the resulting coronary venous CO2 concentration changes. Analysis of the data with a compartmental mass balance model indicated that CO2 washouts and retentions were best fit with a model in which 80% of the myocardial CO2 resides in the interstitial and intracellular compartments and the remaining 20% in vascular compartments. The maximal diffusional trapping compatible with the data resulted in a modest end-capillary-to-end-venous CO2 concentration ratio of 1.02 to 1.04 at resting coronary flows. It is concluded that diffusional trapping of myocardial CO2 was below the detection limits of the experiment and that at normal coronary blood flow rates there is little CO2 diffusional trapping.
Effects of albumin concentration on endothelial albumin transport in vitro
Authors: Shasby D. M. , Peterson M. W.
Published: December 2017

Albumin transfer across cultured porcine pulmonary artery endothelial cell monolayers was studied at different concentrations of luminal and interstitial albumin. Increased interstitial and luminal albumin concentrations increased the rates of transfer of albumin from interstitium to lumen and lumen to interstitium, respectively. Interstitial-to-luminal albumin clearance reached a maximum rate at 725 microM interstitial albumin. The clearance of dextran from interstitium to lumen also increased when interstitial-to-luminal albumin clearance increased, suggesting that albumin was not transferred alone across the endothelium. The increase in interstitial-to-luminal albumin clearance did not occur in the absence of endothelial cells, at 4 degrees C, or when dextran or dextran sulfate sodium were added to the interstitial compartment. These data demonstrate that albumin concentrations can influence the rates of endothelial albumin transfer and that albumin can be transported across the endothelium by a process mediated by endothelial cells.
Metabolism and electrophysiology in subendocardial Purkinje fibers after infarction
Authors: Lurie K. G. , Argentieri T. M. , Sheldon J. , Frame L. H. , Matschinsky F. M.
Published: December 2017

Subendocardial Purkinje fibers (SEPF) have been implicated in the genesis of fatal arrhythmias that occur 24-48 h after infarction but little is known about the metabolic processes involved. Quantitative microchemical and electrophysiological studies were performed on normal and infarcted hearts removed 24 h after coronary artery occlusion. ATP, ADP, AMP, total adenine nucleotide content, phosphocreatine (PCr), and inorganic phosphate in superficial subendocardial Purkinje fibers from infarct preparations decreased approximately 30% compared with normal preparations. The phosphate potential decreased 45% in the infarct group. Similar changes were observed in adjacent contractile muscle between normals and infarcts. Action potentials of SEPF from infarct hearts had increased automaticity, markedly prolonged action potential durations at 50 and 90% repolarization (APD50 or APD90), but unchanged resting membrane potentials. The decrease in ATP, total adenine nucleotides, and the phosphate potential correlated linearly with APD50 and APD90. No correlation was found between PCr and APD90. This combined biochemical and electrophysiological approach provides a promising new way to further probe the biochemical basis of the abnormal electrical properties of subendocardial Purkinje fibers after myocardial infarction.
Hemodynamic fluctuations and baroreflex sensitivity in humans: a beat-to-beat model
Authors: deBoer R. W. , Karemaker J. M. , Strackee J.
Published: December 2017

A beat-to-beat model of the cardiovascular system is developed to study the spontaneous short-term variability in arterial blood pressure (BP) and heart rate (HR) data from humans at rest. The model consists of a set of difference equations representing the following mechanisms: 1) control of HR and peripheral resistance by the baroreflex, 2) Windkessel properties of the systemic arterial tree, 3) contractile properties of the myocardium (Starling's law and restitution), and 4) mechanical effects of respiration on BP. The model is tested by comparing power spectra and cross spectra of simulated data from the model with spectra of actual data from resting subjects. To make spectra from simulated data and from actual data tally, it must be assumed that respiratory sinus arrhythmia at rest is caused by the conversion of respiratory BP variability into HR variability by the fast, vagally mediated baroreflex. The so-called 10-s rhythm in HR and BP appears as a resonance phenomenon due to the delay in the sympathetic control loop of the baroreflex. The simulated response of the model to an imposed increase of BP is shown to correspond with the BP and HR response in patients after administration of a BP-increasing drug, such as phenylephrine. It is concluded that the model correctly describes a number of important features of the cardiovascular system. Mathematical properties of the difference-equation model are discussed.