bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperemic response of the coronary circulation to brief diastolic occlusion in the conscious dog.
Authors: Schwartz G G , McHale P A , Greenfield J C
Published: June 2012

This study was undertaken to determine whether coronary blood flow can be regulated in response to coronary arterial occlusions briefer than a single diastole. The possible involvement of metabolic vs. myogenic mechanisms in such regulation was investigated. Eleven conscious dogs with experimentally produced complete heart block, chronically implanted electromagnetic flow probes, and pneumatic occluders on the left circumflex coronary artery were studied. Diastolic coronary occlusions lasting 100 to 400 msec were performed at paced heart rates of 40, 60, and 120 beats/min. At a heart rate of 60 beats/min, a 200-msec occlusion was sufficiently long to produce a significant reactive hyperemic response; 400-mec occlusions resulted in larger responses, while 100-msec occlusions did not generate a discernible response. The onset of reactive hyperemia was delayed from the end of the occlusion until the first post-occlusion systole. The length of this delay could be altered by changing the heart rate or occlusion duration, but no significant response was detected before the first post-occlusion systole. This characteristic of the data is more consistent with a metabolic than with a myogenic mechanism. If the response is metabolic, the data demonstrate that autoregulation of coronary flow by such a mechanism is very rapid, occurring during the first systole in which a flow deficit is detected by the myocardium.
Microcirculation of left atrial muscle, cerebral cortex and mesentery of the cat. A comparative analysis.
Authors: Chang B L , Yamakawa T , Nuccio J , Pace R , Bing R J
Published: June 2012

By means of transillumination (microtransilluminator and light pipe), comparative analyses were carried out on geometry, topography, and morphometry of microcirculation in the cerebral cortex, left atrial muscle, and mesentery of the cat using computer analysis. In addition, specific types of capillary distribution (concurrent, countercurrent, and asymmetric distribution) in these three organs were ascertained from images visualized on films. These parameters were related to their role in tissue oxygen supply. It was found that mean capillary diameter, mean intercapillary distance, total capillary length, and total capillary surface area differed significantly among the three organs. Differences in mean capillary tortuosity between cerebral and left atrial muscle and between left atrial muscle and mesentery also were significant. Mean capillary tortuosity in mesentery and cerebral cortex was of equal magnitude. In the cerebral cortex, a high degree of tortuosity and asymmetric capillary distribution favor tissue oxygenation. A similar situation exists in left atrial muscle, although some concurrent and countercurrent distribution could be detected. In the mesentery, the combination of high capillary tortuosity and concurrent capillary arrangement is unfavorable for tissue oxygenation.
The effects of the coronary capacitance on the interpretation of diastolic pressure-flow relationships.
Authors: Eng C , Jentzer J H , Kirk E S
Published: June 2012

The effects of coronary capacitance on instantaneous pressure-flow (P/F) relationships were analyzed using a theoretical model of coronary flow during diastole that included capacitance. The magnitude of the discrepancy between actual intramural and instantaneously derived P/F relationships was predicted to be dependent on the ratio of two natural decay constants (central aortic decay constant/intrinsic coronary decay constant). The effects of coronary capacitance are eliminated using constant pressure conditions. The instantaneous (dynamic) and constant pressure (static) P/F relationships were compared experimentally using a reservoir to provide constant pressure perfusion during prolonged diastoles in heart blocked dogs. In the presence of coronary tone, zero flow pressure intercepts (Pzf) of 27.1 +/- 6.6 and 11.0 +/- 3.0 mm Hg were obtained under dynamic and constant pressure conditions respectively, P less than 0.001. After maximal vasodilation, Pzf of 14.2 +/- 4.5 mmHg and 10.7 +/- 2.4 mmHg were obtained under dynamic and constant pressure conditions, respectively, P = NS. Pzf derived under constant pressure conditions were independent of the state of coronary vasomotor tone with a value about 11 mmHg. The slopes of the dynamic P/F relationships tended to be greater than those derived from constant pressure conditions. This may suggest an additional component of increasing coronary resistance during diastole that could not be readily assessed under dynamic conditions. We conclude that coronary capacitive effects and resistance changes during diastole severely limit the interpretation of instantaneous dynamic P/F relationships. Diastolic coronary perfusion ceases at about 11 mm Hg and is independent of coronary tone when capacitive effects are eliminated.
Mechanisms of quinidine-induced depression of maximum upstroke velocity in ovine cardiac Purkinje fibers.
Authors: Weld F M , Coromilas J , Rottman J N , Bigger J T
Published: June 2012

A major advance in understanding how quinidine depresses maximum upstroke velocity (Vmax) is the Hondeghem-Katzung mathematical model which incorporates voltage-independent rate constants for binding to and unbinding from resting, open, and inactive Na channels, and a voltage shift of -40 mV for the Hodgkin-Huxley h-kinetics of quinidine-associated Na channels. Using a double microelectrode voltage clamp technique to control transmembrane voltage and apply conditioning pulses, we found that quinidine blockade increased as transmembrane voltage became more positive in the range -60 to +40 mV, and that the rate of quinidine dissociation increased as transmembrane voltage became more negative in the range -60 to -140 mV. The relationship of Vmax to transmembrane voltage obtained at drive cycles from 500 msec to 20 seconds conformed to the model modified to include voltage-dependent rate constants without the postulated -40-mV shift for quinidine-associated channels. Thus binding of quinidine to inactive Na channels and unbinding from resting channels are both voltage-dependent and can explain frequency and voltage dependent actions of quinidine on Vmax without any voltage shift for quinidine-associated channels.
Stimulation of renin release by hyperoncotic perfusion of the isolated rat kidney.
Authors: Cohen A J , Spokes K , Brown R S , Stoff J S , Silva P
Published: June 2012

Renin release was measured in the isolated rat kidney perfused with a recirculating artificial medium containing bovine serum albumin at 6.7 g per 100 ml of 11 g per 100 ml. At the higher concentration of albumin, glomerular filtration ceased and the rate of renin release over 70 minutes of perfusion was increased 6-fold. The addition of ouabain to the perfusate containing 11 g per 100 ml inhibited the release of renin, suggesting that inhibition of Na-K-ATPase or the related changes in cellular volume or composition prevented renin release. Lowering the osmolality of the perfusate by reducing the concentration of sodium chloride also prevented the increase in renin secretion produced by perfusion with 11 g per 100 ml albumin. Increasing the osmolality of the perfusate with mannitol restored the augmented renin release. These results are consistent with the hypothesis that alterations in the volume of certain cells, perhaps in the juxtaglomerular apparatus itself, can control renin release.
Critical closure in the canine pulmonary vasculature.
Authors: Graham R , Skoog C , Oppenheimer L , Rabson J , Goldberg H S
Published: June 2012

The vascular pressure-flow (P-Q) relationships in zone II (West et al.) were studied in isolated canine left lower lobes, in order to characterize the total resistance in the pulmonary vascular bed with respect to incremental or flow resistance and critical closure. At each of five levels of static lung inflation, the P-Q relationship was curvilinear at low flow and rectilinear at higher flows. The slope of the linear portion was not significantly different at alveolar pressures (PA) = 5, 7, or 9 cm H2O, but decreased significantly at PA = 11 and 15 cm H2O ((P less than 0.05), indicating an increase in flow resistance. The pulmonary artery pressure (Ppa) fell to the same value at zero flow regardless of inflation level [10.1 +/- 1.0 (SD) cm H2O at PA = 5 cm H2O to 10.9 +/- 2.7 (SD) at PA = 15 cm H2O]. The Ppa intercept (Ppai), extrapolated from the linear portion of the P-Q curve and representing the average closing pressure for the vascular bed, increased from 16.0 +/- 1.8 (SD) cm H2O at PA = 5.0 to 26.5 +/- 4.4 (SD) cm H2O at PA = 15 (P less than 0.05) in a direct one-to-one relationship with the increase in PA. Since this results in a constant transmural gradient at the alveolar vessel level, these vessels must be the major fraction which undergo critical closure. Operationally defined vascular compliance, determined from the slope of a simultaneously obtained pressure-volume (P-V) curve, decreased significantly from 1.51 +/- 0.62 (SD) ml/cm H2O at PA = 5.0 H2O to 0.87 +/- 0.27 ml/cm H2O at PA = 15 cm H2O (P less than 0.05).
Effect of outflow pressure upon lymph flow from dog lungs.
Authors: Drake R E , Adcock D K , Scott R L , Gabel J C
Published: June 2012

The pulmonary lymph flow rate (QL) should be a function of the lymph vessels' resistance and the pressure gradient along the vessels. We attempted to study how these factors affect lymph flow. We assumed that the lymph system could be represented by a single pressure generated within the lung (PL) and a single resistance (RL). Thus, QL should be a function of the lymph vessel outflow pressure (Po): QL = (PL - Po)/RL. We cannulated tracheobronchial lymph vessels in eight anesthetized dogs and varied Po by raising the outflow end of the cannula. QL decreased linearly when we increased Po. We estimated RL as - delta Po/ delta QL and PL as the extrapolated Po at which QL = 0. At baseline PL = 7.7 +/- 2.7 (SD) cm H2O and RL = 0.36 +/- 0.25 cm H2O. min/microliters. After we increased capillary pressure to produce edema, PL and RL averaged 22.8 +/- 8.8 and 0.14 +/- 0.12, respectively. After we reduced the capillary pressure to baseline in the edematous lungs, PL and RL averaged 11.6 +/- 2.8 and 0.08 +/- 0.09, respectively. All changes in PL and RL were significant (P less than 0.05). These results show that (1) lymph flow rate depends upon lymph vessel outflow pressure, and (2) the QL vs. Po relationship is changed by edema. PL may be equal to the pressure causing lymph to flow and RL may equal the lymph vessel resistance.
Autoregulation of blood flow within individual arterioles in the rat cremaster muscle.
Authors: Morff R J , Granger H J
Published: June 2012

Autoregulatory responses to alterations in arterial or venous perfusion pressure were determined for individual arterioles within the rat cremaster muscle. The cremaster muscle of pentobarbital anesthetized rats (50 mg/kg, ip) was surgically exposed and maintained in a controlled tissue bath for visualization by in vitro television microscopy. Cremaster bath PO2 was controlled at either a high (approximately 70 mm Hg) or low (approximately 19 mm Hg) level. Inside diameter and red blood cell velocity were measured for individual first (1A), second (2A), or third (3A) branching order arterioles, and instantaneous blood flows within each arteriole were calculated. To measure the autoregulatory responses, we decreased arterial perfusion pressure to the microvascular bed by gradually occluding the sacral aorta. Significant autoregulation was observed in all orders of vessels, but, in general, autoregulation was more pronounced at all vessel levels when bath PO2 was low, and the autoregulatory gain was greater for the smaller vessels compared to the larger vessels. Elevation of venous pressure within the vascular bed by gradual occlusion of the inferior vena cava led to a significant vasoconstriction of the smaller vessels, suggesting that a significant myogenic component was present. The vasoconstriction response to elevated venous pressure was more pronounced when bath PO2 was high. Our data are not consistent with a purely myogenic or purely metabolic mechanism, but suggest that both mechanisms are simultaneously contributing to the local vascular regulation.
Optimal hematocrit for oxygenation of canine intestine.
Authors: Shepherd A P , Riedel G L
Published: June 2012

To determine the direct effects of hematocrit on intestinal oxygen consumption and to determine whether an optimal hematocrit exists for intestinal oxygenation, we perfused isolated canine gut loops at a constant pressure (120 mm Hg) and varied hematocrit from 80% to 10%. As hematocrit fell, blood flow rose while arterial oxygen content fell. The regression of blood flow on hematocrit was linear, whereas the relationship between oxygen uptake and hematocrit was parabolic, showing a maximal oxygen uptake at an hematocrit of 48.7%. To determine whether the optimal hematocrit for intestinal oxygenation could be altered by changes in vasomotor tone, we performed two other series of experiments. Raising perfusion pressure to 180 mm Hg did not significantly alter the optimal hematocrit for oxygen uptake. However, when we increased the oxygen demands of the gut by placing transportable solutes within the intestinal lumen, the optimal hematocrit for oxygen uptake increased markedly. We conclude that the optimal hematocrit for intestinal oxygenation is slightly higher than the normal range, a finding that could possibly be explained by the plasma skimming known to occur in the intestinal mucosa. Our experimental design and method of data analysis could be used to determine the optimal hematocrit in other organs.
Alterations in vascular smooth muscle mass in the spontaneously hypertensive rat. Role of cellular hypertrophy, hyperploidy, and hyperplasia.
Authors: Owens G K , Schwartz S M
Published: June 2012

In a previous brief report we demonstrated that differences in aortic smooth muscle mass between spontaneously hypertensive and Wistar-Kyoto rats were due to smooth muscle cell hypertrophy, without hyperplasia. Smooth muscle cell hypertrophy, however, was accompanied by an increase in the frequency of polyploid cells. This study reports (1) the relationship between changes in smooth muscle cell mass and DNA ploidy, (2) the proportion of the increase in mass of smooth muscle in spontaneously hypertensive rats that can be accounted for by polyploid cells, and (3) the time-course of changes in ploidy during the development of hypertension. Flow microfluorimetric and Feulgen-DNA microspectrophotometric measurements demonstrated that the frequency of polyploid smooth muscle cells was 2-3 times greater in spontaneously hypertensive rats than in Wistar-Kyoto rats at 3 months of age and older. The frequency of polyploid cells increased with age and level of blood pressure. No differences in the frequency of polyploid cells were apparent between prehypertensive 1-month spontaneously hypertensive and Wistar-Kyoto rats. By cytospectrophotometric analysis, spontaneously hypertensive rat diploid, tetraploid, and octaploid smooth muscle cells had 36%, 136%, and 377%, respectively, the protein content of Wistar-Kyoto rat diploid cells. The increase in mean cellular protein (53% by cystospectrophotometry) in spontaneously hypertensive rats could account for the total increase (56%) in aortic smooth muscle mass, measured by morphometry. Thus, smooth muscle cell hypertrophy alone can account for the increased mass of smooth muscle in spontaneously hypertensive rat aortas, while the majority of change in smooth muscle mass is due to the increased frequency and mass of polyploid cells.
Angiotensin II receptors on human platelets.
Authors: Moore T J , Williams G H
Published: June 2012

The investigation of the interaction between angiotensin II and its receptors in human subjects has been hampered by the inaccessibility of human tissue containing angiotensin II receptors. In order to find a more accessible angiotensin II-binding tissue, we studied angiotensin II binding to platelets in normal human volunteers. Platelet preparations purified on Ficoll: Isopaque gradients were incubated with 125I-angiotensin II (30 pm), with and without unlabeled angiotensin at 22 degrees C, separating bound from free hormone by microcentrifugation. Binding was linearly related to the number of platelets incubated, and, at 8 X 10(5) cells/microliters, specific binding ranged from 0.8 to 10%. Scatchard analysis indicated a binding site with a Kd of 2.4 +/- 0.3 X 10(-10) m which agreed well with the Kd by displacement analysis (3.1 X 10(-10) m). The relative binding potencies for angiotensin II and analogues were: angiotensin II = des-Asp1 an angiotensin II greater than [Sar1, Ala8] angiotensin II greater than des-Asp1-[Ile8] angiotensin II greater than angiotensin I. The effect of high and low sodium (Na) intake (200 vs. 10 mEq/day) on platelet angiotensin II binding was studied in nine subjects. Compared to low Na, high Na intake produced an 80% increase in the angiotensin II-binding capacity (P less than 0.01) with no significant change in binding affinity. We conclude that human platelets possess angiotensin receptors whose binding characteristics and modulation by dietary sodium resemble the properties of the receptors on "classical" animal angiotensin target tissues. The platelet may provide an accessible source of angiotensin receptors for a detailed study of angiotensin-receptor interaction in human tissue.
Rat cardiac muscle single cell automaticity responses to alpha- and beta-adrenergic agonists and antagonists.
Authors: Hermsmeyer K , Mason R , Griffen S H , Becker P
Published: June 2012

Isolated cardiac muscle cells from neonatal rat ventricular myocardium have both alpha- and beta-adrenergic, positive chronotropic responses, with sensitivity to applied adrenergic agents more than 100 times greater than the intact neonatal heart. These highly sensitive isolated single cells and small groups of cells also reveal partial agonist activity of the alpha-adrenergic antagonist, phentolamine, and the beta-adrenergic antagonist, propranolol. The most likely explanation for the high sensitivity is the lack of a desensitization process that could involve both a desensitization substance and changes in receptors. These experiments suggest that all adrenergic antagonists could possibly show partial agonist activity.
Effects of diuretics on inner medullary hemodynamics in the dog.
Authors: Spitalewitz S , Chou S Y , Faubert P F , Porush J G
Published: June 2012

Although the hemodynamic effects of diuretics have been studied extensively, their effects on inner medullary blood flow remain unknown. In the present study, renal hemodynamics, including papillary plasma flow measured by the albumin accumulation technique, and associated alterations in papillary tissue solute content were determined in anesthetized, hydropenic dogs and during euvolemic diuresis induced by furosemide (3 mg/kg plus 2 mg/kg per hr, iv), ethacrynic acid (3 mg/kg plus 2 mg/kg per hr, iv) or chlorothiazide (10 mg/kg plus 10 mg/kg per hr, iv). Renal blood flow increased significantly after furosemide and ethacrynic acid and decreased significantly after chlorothiazide. Sixty minutes after diuretic administration, papillary plasma flow was 10.8 +/- 1.0 (mean +/- SE) in six furosemide- and 11.3 +/- 2.6 ml/min per 100 g in six ethacrynic acid-treated dogs, both significantly lower than in eight normal or eight chlorothiazide-treated dogs [26.4 +/- 2.6 and 26.7 +/- 2.7 ml/min per 100 g, respectively (P less than 0.01)]. A similarly low papillary plasma flow was also noted 10 minutes after diuretic administration in five furosemide and four ethacrynic acid dogs (13.6 +/- 2.3 and 13.4 +/- 1.8 ml/min per 100 g, respectively). In furosemide and ethacrynic acid dogs, papillary osmolality and sodium content were significantly lower than those in normal or chlorothiazide dogs. In normal and chlorothiazide dogs, papillary sodium content was similar, with a significantly reduced papillary osmolality in the latter. At the time papillary plasma flow was measured, extracellular fluid volume was similar among the four groups of dogs; however, plasma renin activity increased significantly in furosemide and ethacrynic acid dogs (P less than 0.01) and remained unchanged in normal and chlorothiazide dogs. Furthermore, papillary plasma flow was restored to normal (25.3 +/- 3.9 ml/min per 100 g) in five dogs in which furosemide was infused during angiotensin II blockage with saralasin, despite a similar diuresis and natriuresis as the other furosemide group. These data demonstrate that after administration of furosemide, ethacrynic acid and chlorothiazide, regulation of papillary plasma flow is independent of renal blood flow, and suggest that angiotensin II may play a role in the reduced papillary plasma flow in furosemide and ethacrynic acid dogs.
A neural factor involved in increase of the glycogen phosphorylase activity after coronary ligation in both ischemic and nonischemic areas of the dog heart.
Authors: Sakai K , Abiko Y
Published: June 2012

We performed experiments to determine whether or not extracardiac factors are involved in the increase of the glycogen phosphorylase activity after coronary artery ligation in dog hearts. A branch of the left anterior descending coronary artery (LAD) was ligated for 1.5 minutes. The glycogen phosphorylase activity was determined in the endo- and epicardial layers. LAD ligation significantly increased the glycogen phosphorylase activity in both LAD (ischemic) and circumflex (nonischemic) areas. Pretreatment with reserpine (1 mg/kg, im, 24 hours before experiments) or hexamethonium (3 mg/kg, iv) prevented the LAD ligation-induced increase in the glycogen phosphorylase activity, but adrenalectomy did not. In the heart-lung preparation and stellectomized dogs, LAD ligation did not increase the glycogen phosphorylase activity in both ischemic and nonischemic areas. Changes in the glycogen phosphorylase activity in the endocardial layers were not essentially different from those in the epicardial layers. In other dogs, metabolic intermediates and ST segment of the surface electrocardiogram were measured. LAD ligation significantly decreased the tissue level of creatine phosphate and increased that of lactate in the ischemic but not in the nonischemic area. An elevation of ST segment occurred only in the ischemic area. Thus ischemic and nonischemic areas were confirmed. The ATP level, however, did not change in any of the ischemic and nonischemic areas. It is suggested that LAD ligation increases the glycogen phosphorylase activity in both ischemic and nonischemic areas probably by an increase in the efferent cardiac sympathetic nerve activity.
Effects of ouabain and vagal stimulation on sinus nodal function in conscious dogs.
Authors: Hariman R J , Hoffman B F
Published: June 2012

We studied the effects of intravenous ouabain administration (15 micrograms/kg) and vagal stimulation on instrumented conscious dogs. In these dogs, a special electrode was implanted on the epicardial surface over the sinus node and plaque electrodes were placed on the superior vena cava and left atrial appendage. Unipolar sinus electrograms were recorded through the terminals of the sinus electrode paired with the superior vena caval electrode. An electrode also was implanted around the desheathed cervical vagosympathetic trunk, and a coiled polyethylene tube with side holes was implanted cranial to it. Ouabain administration resulted in: (1) an increase in the sinus cycle lengths and sinoatrial intervals and increase in beat-to-beat variation of the sinus cycles and sinoatrial intervals, and (2) periods of sinus pacemaker shift, sinus arrest and sinoatrial block that occurred spontaneously or after atrial overdrive stimulation delivered through the electrode on the left atrial appendage. These effects of ouabain were abolished by intravenous administration of atropine (2 mg). Prior to vagal stimulation, intravenous propranolol (0.5 mg/kg) was administered to block sympathetic responses and 0.75% bupivacaine was injected through the polyethylene tube to block afferent transmission. Vagal stimulation in conscious dogs resulted in two types of responses: (1) slowing of sinus pacemaker rate accompanied by a decrease in diastolic slope and followed by sinus pacemaker shifts, and (2) gradual prolongation of the sinoatrial intervals followed by failure of sinoatrial conduction. An intravenous bolus of acetylcholine (0.1 mg) resulted in a response of type 2 in dogs in which vagal stimulation produced a response of type 1. The marked similarity between the effects of ouabain and vagal stimulation on sinus function and the abolition of the effects of ouabain by atropine suggest that the ouabain effects are vagally mediated.
Histochemical detection of specific isozymes of myosin in rat ventricular cells.
Authors: Weisberg A , Winegrad S , Tucker M , McClellan G
Published: June 2012

A histochemical method for distinguishing isozymes of myosin in rat ventricles has been developed. The procedure involves preincubation in pH 10.5, which inhibits Ca-activated ATPase of the V3 isozyme but not the V1 isozyme of myosin. The specificity of the technique has been demonstrated by comparison of results in hearts from young euthyroid and hypothyroid rats, in which the predominant isozymes are, respectively, V1 and V3. The technique is capable of detecting as small a change in the relative amount of V1 as 15% of the total myosin. Isoenzymes appear to be uniformly distributed within each ventricular cell. There is only a small difference in the content of V1 among the cells in a ventricular chamber of hearts from young euthyroid and hypothyroid rats, but in the period of rapid transition of isozyme content after thyroidectomy, there is considerable heterogeneity of V1 concentration among the cells. The functional implications of the mixture of isozymes is discussed.
Thromboxane synthesis by sources other than platelets in association with complement-induced pulmonary leukostasis and pulmonary hypertension in sheep.
Authors: McDonald J W , Ali M , Morgan E , Townsend E R , Cooper J D
Published: June 2012

Infusion into sheep of plasma containing zymosan-activated complement produces leukopenia, pulmonary leukostasis, and pulmonary artery hypertension. We previously demonstrated a close relationship between the pulmonary vascular response and elevations of plasma thromboxane. We have investigated the source of thromboxane synthesis in this model. Plasma containing zymosan-activated complement added to whole blood did not stimulate thromboxane synthesis. This observation suggested that leukocytes do not synthesize thromboxane directly in response to complement added to whole blood did not stimulate thromboxane synthesis. This observation suggested that leukocytes do not synthesize thromboxane directly in response to complement. Sheep rendered severely thrombocytopenic by the administration of antiplatelet serum responded to complement infusion in the usual way. Pretreatment with aspirin (10 mg/kg) protected sheep against the pulmonary vascular response and completely blocked thromboxane synthesis. Transfusion of functional platelets did not restore these responses. Twenty-four hours after aspirin treatment, in vivo thromboxane synthesis was significantly greater than platelet thromboxane synthesis in vitro. Thromboxane is synthesized by a tissue which recovers cyclooxygenase enzyme activity at a rate that is more rapid than platelet turnover. Sheep lung synthesizes thromboxane actively in vitro. It is postulated that leukocytes exposed to activated complement components damage pulmonary vascular endothelial cells and stimulate synthesis of thromboxane A2 which causes pulmonary vasoconstriction.
Effect of regional ischemia on the left ventricular end-systolic pressure-volume relationship of isolated canine hearts.
Authors: Sunagawa K , Maughan W L , Sagawa K
Published: June 2012

We studied the effects of regional ischemia on the left ventricular isovolumic end-systolic pressure-volume relationship (ESPVR) in six excised, blood-perfused canine ventricles. We created different extents of regional ischemia by ligating various branches of the coronary arteries while keeping the coronary arterial pressure constant (80 mm Hg). The extent of regional ischemia (Rm) relative to the total mass of the left ventricular myocardium was determined by regional myocardial blood flow measured by the radioactive microsphere technique. With regional ischemia, the ESPVR shifted rightward without significant change in slope in the physiologic end-systolic pressure range. In the subphysiological end-systolic pressure range, however, its slope became lower than control. In order to quantify the degree of the rightward shift, we measured the extrapolated volume axis intercept (Vo) by fitting a straight line to the ESPVR in the physiological range under control and ischemic conditions. The shift in Vo (delta Vo) associated with ischemia was linearly correlated with Rm (delta Vo = 50.7Rm-0.6, n = 28, r = 0.944, P less than 0.001). We conclude that the major effect of acute regional ischemia on the ESPVR in the physiological pressure range is a parallel rightward shift. This forms a striking contrast to the effect of global ischemia (under which only the slope is affected without a substantial change in Vo).
The relationship of human atrial cellular electrophysiology to clinical function and ultrastructure.
Authors: Mary-Rabine L , Albert A , Pham T D , Hordof A , Fenoglio J J , Malm J R , Rosen M R
Published: June 2012

Although previous studies have described the electrophysiological and ultrastructural characteristics of human cardiac fibers, no attempt has been made as yet to describe quantitatively the relationship between the ultrastructural and cellular electrophysiological derangements occurring with cardiac disease, and their clinical manifestations. In this study, we used standard microelectrode techniques to record the action potential characteristics of human atrial fibers obtained during cardiac surgery and correlated the electrophysiological parameters with clinical and ultrastructural data. Ultrastructure was studied by optical and electron microscopy. We found a multiple linear regression among maximum diastolic potential, atrial size and pressure, P wave duration and ultrastructure changes. Proliferations of Z band material, widening of intercalated discs, and degenerative changes were quantified and correlated with electrophysiological and clinical data. These studies emphasize the relationship between hemodynamic anomalies and resultant changes in both human atrial fiber structure and electrical function. Finally, the likelihood of occurrence of arrhythmias can be predicted using the analytic method described.
Heterogeneity of the action potential in isolated rat ventricular myocytes and tissue.
Authors: Watanabe T , Delbridge L M , Bustamante J O , McDonald T F
Published: June 2012

The objectives of this study were to measure action potential parameters in enzyme-dissociated, adult rat ventricular myocytes stimulated at 1 Hz, to compare these measurements with those obtained from intact ventricular tissue, and to determine myocyte and tissue responses at stimulus frequencies between 0.1 and 5 Hz. Action potentials were characterized in terms of amplitude, overshoot, resting potential, duration at 25% and 75% repolarization (APD25, APD75), and Vmax. Based on statistical differences in APD25 and APD75, myocyte action potentials were classified as type I (3.1 +/- 1.0 and 21.5 +/- 3.6 msec), type II (7.4 +/- 1.1 and 38.2 +/- 6.7 msec), or type III (14.5 +/- 1.9 and 46.0 +/- 4.1 msec). Action potentials corresponding to type I were found in right ventricular endocardium and right papillary muscles, and those corresponding to types II and III in the left ventricular endocardium [apex, middle (II); base (III)] and left papillary muscles (II). Myocytes and papillary muscles responded to increases in driving rate with nearly identical lengthening of APD25 and shortening of APD75. The one exception was at 5 Hz where a lengthening of the APD75 occurred in some myocytes. We conclude that action potential configuration in rat ventricle is heterogeneous, and that this is reflected by the different types of action potentials in isolated myocytes. It is likely that the magnitude of a transient outward current is a determinant of action potential configuration, and that slow reactivation of this current is a significant factor underlying the stimulus frequency response.
Contribution of alpha-adrenoceptor activation to the pathogenesis of norepinephrine cardiomyopathy.
Authors: Downing S E , Lee J C
Published: June 2012

Graded doses of norepinephrine and methoxamine were given to rabbits over a standard 90-minute infusion period to assess their potential for inducing myocardial injury. Lesions of myofiber necrosis and leukocytic infiltration were graded semiquantitatively in animals killed 2 days later. A close correlation was found between the dose of norepinephrine and the histological score (r = 0.912, P less than 0.001). Mean arterial pressure rose from 100 mm Hg to a maximum of 129 mm Hg, and averaged 115 mm Hg during infusion of 2 micrograms/min per kg. However, heart rate fell from 287 beats/min to average 208 beats/min. The pressure-rate product, an index of metabolic demand, showed no significant change and did not differ from saline-infused controls. Beta-adrenergic blockade with practolol (4 mg/kg) or propranolol (1 mg/kg) failed to significantly reduce cardiac injury with norepinephrine. However, alpha-adrenoceptor blockade with phentolamine (10 mg), alone or in combination with either of the beta-antagonists, markedly reduced lesion formation as reflected by the histological score (P less than 0.02). Administration of the alpha-agonist methoxamine produced dose-related increases in the intensity of myocardial injury (r = 0.938, P less than 0.01), morphologically identical with those resulting from norepinephrine. Hemodynamic changes also were comparable. Phentolamine markedly reduced methoxamine injury. It may be concluded from these studies that norepinephrine cardiomyopathy results in large part from activation of the alpha-adrenergic system in the rabbit model. Ischemia or a supply-demand mismatch are unlikely mechanisms. We speculate that alterations in myofiber Ca++ translocation, uptake, and binding induced by alpha 1-receptor activation may contribute to membrane damage.
Myocardial metabolites of ethanol.
Authors: Lange L G , Sobel B E
Published: June 2012

Because of the importance of alcohol-induced heart muscle disease and the obscurity of its pathogenesis, this study was undertaken to determine whether fatty acid ethyl esters, myocardial metabolites of ethanol recently described in our laboratory to be synthesized in cell-free extracts of rabbit myocardium, accumulate in hearts of human subjects exposed to ethanol in vivo. Lipid extracts were prepared from left ventricular samples obtained at necropsy from six subjects who had been exposed to ethanol acutely or chronically. Fatty acid ethyl esters were present in each extract in concentrations ranging from 9 to 115 microM. In contrast, they were consistently absent from analogous samples obtained from hearts of abstainers (n = 5). In parallel studies in experimental animals, we found that fatty acid ethyl esters are formed not only in the heart but also in the pancreas and liver--targets of injury associated with chronic alcohol abuse. These results demonstrate the presence in human myocardium of a novel metabolite of ethanol that potentially may serve as a marker for exposure to alcohol and that could be relevant to the pathophysiology of excessive alcohol consumption leading to cardiac abnormalities.
Increased arterial pressure variability after arterial baroreceptor denervation in fetal lambs.
Authors: Yardley R W , Bowes G , Wilkinson M , Cannata J P , Maloney J E , Ritchie B C , Walker A M
Published: June 2012

Baroreceptor reflexes can be demonstrated during fetal life, but whether baroreceptors normally regulate fetal arterial pressure is unknown. This problem was addressed directly by measuring arterial pressure and analyzing its variation in eight unanesthetized fetal lambs throughout the last third of gestation, and comparing these data with similar measurements made in seven fetal lambs with denervated arterial baroreceptors. Measurements were made at 5-minute intervals over 24 hours in a total of thirty-three experiments. The coefficient of variation of mean arterial pressure (standard deviation of mean arterial pressure/mean value of mean arterial pressure) expressed as a percentage was used as an index of blood pressure variability. Coefficients averaged 7.0% in intact lambs and 12.1% in barodenervated lambs (P less than 0.001), signifying considerably increased variability of mean arterial pressure after barodenervation. Mean arterial pressure averaged over 24 hours was not different between the two groups prior to 120 days (0.8) of gestation. Between 120 days and term, mean pressure was significantly greater in the denervated fetuses (65 cm H2O) than in the sham-operated controls (60 cm H2O, P less than 0.025). These data demonstrate that a baroreceptor-blood pressure reflex functions during late gestational development in lambs and signify an important role of arterial baroreceptors in regulating fetal arterial pressure. Failure to regulate arterial pressure in the barodenervated fetus could result in significant alterations in placental perfusion and exchange, and in the regional delivery of oxygen and substrates to developing organs in these animals.
Baroreflex control of the circulation in chronically instrumented fetal lambs.
Authors: Itskovitz J , LaGamma E F , Rudolph A M
Published: June 2012

The role of the arterial baroreceptors in regulating the fetal circulation was studied in 18 chronically instrumented fetal lambs, 120-136 days gestation. The results were compared to those obtained in three sinoaortic denervated adult sheep. Nine fetuses underwent sinoaortic denervation and nine fetuses served as sham-operated controls. Two to 3 days after surgery, heart rate and blood pressure were recorded continuously and analyzed over 1-hour periods. In the denervated fetuses, marked fluctuations of the arterial pressure and heart rate were observed. Frequency distribution curves for mean arterial pressure and heart rate showed broader and flatter curves in the denervated fetuses. The average mean arterial pressure and heart rate were not significantly different between the two groups. However, the standard deviation as an index of variability of the mean arterial pressure increased from 2.7 +/- 0.9 (mean +/- standard deviation) in the control group to 6.5 +/- 2.4 in the denervated fetuses, and the standard deviation of the heart rate increased from 10.6 +/- 2.1 to 21.5 +/- 5.7. In the adult sheep, mean arterial pressure and heart rate increased on the 1st day after denervation and returned to near control values on the 3rd day. The variability of the mean arterial pressure increased, but that of the heart rate did not change. Fetal cardiac output and its distribution were measured by the radionuclide-labeled microsphere technique. Combined ventricular output was not statistically different between the groups, but the blood flow to the fetal body was 27% higher in the denervated fetuses. The calculated fetal body vascular resistance was 31% lower in the denervated lambs. This study indicates that the arterial baroreceptors are important in regulating variability of the arterial pressure and heart rate in fetal life, and also may have a significant role in maintaining the normal peripheral vascular resistance.
Influence of perfusate PO2 on hypoxic pulmonary vasoconstriction in rats.
Authors: Marshall C , Marshall B E
Published: June 2012

The purpose of these studies was to evaluate the influence of perfusate oxygen tension on hypoxic pulmonary vasoconstriction and to identify the site at which both alveolar and perfusate gas tensions stimulate hypoxic pulmonary vasoconstriction. Lungs from adult rats were ventilated and perfused in vitro at constant temperature, PCO2, and pH, with a perfusion circuit incorporating a membrane oxygenator that allowed independent control of the alveolar and perfusate gas tensions. Blood flow to the lung was constant (0.06 ml per g body weight per min), and pulmonary vascular resistance was therefore proportional to pulmonary artery pressure. In study 1, the pulmonary artery pressor response to zero or 22 mm Hg alveolar oxygen was measured when the perfusate oxygen tensions were approximately 8, 26, 41, 64, or 128 mm Hg. The pressor response as a percent of the maximum pressure change was progressively reduced as perfusate oxygen tension increased. For alveolar oxygen tension of zero; the pressor response = 128 -39 (Log PPO2) and r = 0.8 (P less than 0.01), the effect of perfusate gas tension on the response to alveolar gas tension of 22 mm Hg was similar. These results demonstrate that the stimulus for hypoxic pulmonary vasoconstriction is a function of both alveolar and perfusate oxygen tension. In study 2, the response to alveolar oxygen tension of 42 mm Hg was measured with mean perfusate oxygen tensions of 130, 52, and 17 mm Hg. In six animals with forward perfusion, the responses decreased with increasing perfusate oxygen tension, as in study 1. In another six animals, with retrograde perfusion, the responses to alveolar hypoxia were not altered when perfusate oxygen tension was increased. These results demonstrate that the sensor region for hypoxic pulmonary vasoconstriction is precapillary. These studies confirm and extend previous hypotheses that alveolar and perfusate oxygen tensions together, determine the PO2 at a precapillary site to stimulate hypoxic pulmonary vasoconstriction.
Consistent parallel relationships among myocardial oxygen consumption, coronary blood flow, and pericardial infusate adenosine concentration with various interventions and beta-blockade in the dog.
Authors: Knabb R M , Ely S W , Bacchus A N , Rubio R , Berne R M
Published: June 2012

Coronary blood flow responds uniquely to changes in myocardial demand, regardless of the stimulus. If adenosine mediates this response, interstitial fluid adenosine concentration should also change in parallel with myocardial oxygen consumption and coronary blood flow during alterations of cardiac work. We tested this hypothesis by measuring coronary blood flow, myocardial oxygen consumption, and the concentration of adenosine in pericardial infusates, an index of interstitial fluid adenosine concentration, during six experimental conditions and control states in anesthetized, open-chest dogs. Significant alterations of myocardial oxygen consumption and coronary blood flow during aortic constriction, vagal stimulation, atrial pacing, or intravenous infusion of calcium chloride, norepinephrine, or isoproterenol were accompanied by significant alterations in pericardial infusate adenosine concentration. Significant linear relationships were determined among myocardial oxygen consumption, coronary blood flow, and pericardial infusate adenosine concentration for each of the experimental stimuli and their paired control values. There were no significant differences among the six different conditions for any of these relationships. In addition, these relationships were not altered by beta-blockade in five dogs subjected to aortic constriction and calcium infusion. Although beta-blockade may alter the effects of a stimulus, myocardial oxygen consumption, coronary blood flow, and adenosine all are affected proportionately. The results suggest that adenosine production responds to alterations of myocardial oxygen consumption independently of the stimulus which produces the change in oxygen demand, and the resultant change in interstitial fluid adenosine concentration may initiate the change in coronary blood flow to maintain the balance between oxygen supply and demand.
Myosin isoenzymes in normal and hypertrophied human ventricular myocardium.
Authors: Mercadier J J , Bouveret P , Gorza L , Schiaffino S , Clark W A , Zak R , Swynghedauw B , Schwartz K
Published: June 2012

We tested the hypothesis that hypertrophy of the human heart is associated with the redistribution of ventricular isomyosins. Human cardiac myosin was isolated from autopsy samples of left ventricular free wall of patients with cardiac hypertrophy and of fetal, young, and adult subjects without heart disease. The following parameters were studied: electrophoretic migration in denaturing and non-denaturing conditions; immunological cross-reactivities with three different types of antibodies; and early phosphate burst size and steady state ATPase activities stimulated by K+-EDTA, Ca++, Mg++, and actin. The antibodies were chosen for their ability to recognize selectively the rat V1 and V3 cardiac isomyosins. The first type was a monoclonal antibody, CCM-52, prepared against embryonic chick cardiac myosin, the second was an anti-beef atrial myosin, and the third was an anti-rat V1 myosin. CCM-52 reacted with a greater affinity with rat V3 than with rat V1, and was a probe of mammalian V3. Anti-beef atrial myosin and anti-rat V1 myosin both recognized specifically beef atrial and rat V1 myosins, and were thus considered as probes of mammalian V1. Under non-denaturing conditions, human myosins migrated as rat V3 isomyosin; under denaturing conditions, no difference was observed in any of the electrophoretic parameters between all samples tested, except for the fetal hearts which contained a fetal type of light chain. The immunological studies indicated that human myosins were composed mostly of a V3 type (HV3), but contained also some V1 isomyosin. A technique was developed to quantify the amount of human VI isomyosin which was found to range from almost 0 to 15% of total myosin, and to vary from one heart to the other, regardless of the origin of the heart. Enzymatic studies showed no significant difference between normal, hypertrophied, and fetal hearts in any of the activities tested. However, there was a significant correlation between Ca++-stimulated ATPase activities and HV1 amount (at 0.05 M KCl, n = 18, r2 equal 0.49, P less than 0.01; at 0.5 M KCl, n = 18, r 2 = 0.5, P less than 0.01). These data demonstrate the heterogeneity of human ventricular myosin, which appears to be composed, as in other mammalian species, of V1 and V3 isoforms of different ATPase activities (V1 greater than V3). However it seems that V1 to V3 shifts do not appear to be of physiological significance in the adaptation of human heart to chronic mechanical overloads.