bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Digitoxin on Labile and Inorganic Phosphates, Lactate, Glycogen, Potassium and Sodium in Dog Ventricle
Authors: REBAR JOHN , REBAR BLANCHE T. , OMACHI AKIRA
Published: June 2012

This communication deals with the effects produced by digitoxin on the metabolism of the dog's ventricles as indicated by changes in labile and inorganic phosphates, lactate, glycogen, potassium and sodium content of the myocardium immediately frozen after excision. The results suggest increased turnover of high energy phosphate and glycogen by nontoxic doses.
Mixing of Cr
51
-Labeled Red Cells in Patients with Congestive Heart Failure and Controls
Authors: FUNKHOUSER ROBERT K.
Published: June 2012

Composite time-concentration curves of labeled erythrocytes in venous blood constructed by pooling data from 11 patients without circulatory failure showed a curve of mixing lasting 25 min. Data from 9 patients in congestive heart failure showed variable mixing lasting at least as long as in the control patients.
Sympathoadrenal System and Response of Heart to Acute Exchange Anemia
Authors: LOVEGROVE T. D. , GOWDEY C. W. , STEVENSON J.A. F.
Published: June 2012

This report deals with a study of the relative roles that the sympathetic nervous system and adrenal medulla play in the cardiac responses to experimental anemia.
Left ventricular energetics. Heat loss and temperature distribution of canine myocardium.
Authors: ten Velden G H , Elzinga G , Westerhof N
Published: June 2012

The sum of total left ventricular heat loss and left ventricular mean total external power was compared with the product of oxygen consumption and its energy equivalent. Myocardial blood flow, measured with 15 +/- 3 micrometers radioactive microspheres, was multiplied by the transcoronary arteriovenous temperature difference and by oxygen content difference to obtain coronary heat loss and oxygen consumption, respectively. Since only part of the heat is carried away by the coronary system a thermodilution technique was used to obtain the ratio between the heat removed by the coronary system and the external heat loss. A correction was made for the endothermic reactions of hemoglobin deoxygenation and carbon dioxide reactions with blood. Left ventricular oxygen consumption corresponded to 2.26 +/- 0.66 W/100 g, and for the sum of total left, ventricular heat loss and external power, 2.09 +/- 0.51 W/100 g was found (n = 14). In a second series, the measured transmyocardial temperature distribution was compared with the calculated temperature distribution, assuming that heat production in the myocardium is uniform and that heat is lost by coronary flow and diffusion. When thoracic and luminal myocardial surface temperatures were about equal, blood flow was found to be about the same in the various layers of the heart, whereas myocardial temperature was found to be highest near the middle of the wall (0.36 +/ 0.07 degrees C warmer than luminal temperature (n = 6). When thoracic surface temperature was increased or decreased (by + 1.56 +/- 0.99 degrees and -1.10 +/- 0.59 degrees C, respectively), consistent changes were seen for the temperature distribution in the myocardium, but not for the local flow (endo/epi ratio: 1.06 +/- 0.29 and 0.96 +/- 0.21, respectively). These data suggest that myocardial blood flow is independent of tissue temperature.
Comparative sequence of myosin light chains from normal and hypertrophied human hearts.
Authors: Klotz C , Leger J J , Elzinga M
Published: June 2012

Myosin light chains from normal and hypertrophied human hearts were partially sequenced in order to see whether structural modifications of these light subunits could provide a molecular basis for the changes observed in heart properties and in myosin enzymatic activity. Normal light chains were prepared form hearts taken at autopsy, weighing 350 g or less and apparently devoid of myocardial disease. "Hypertrophied cardiac myosin light chains" were prepared from two greatly hypertrophied hearts, weighing 600 and750 g. No amino acid substitutions, deletions, or additions were observed in the light chains from hypertrophied hearts. The third light chain previously reported in human cardiac myosin and related to hypertrophy was found to be a proteolytic product of LC2. The comparison between human and beef cardiac myosin light chains indicated that the sequences of these subunits of the myosin molecule are highly conserved.
Work as a correlate of canine left ventricular oxygen consumption, and the problem of catecholamine oxygen wasting.
Authors: Rooke G A , Feigl E O
Published: June 2012

Neither stroke volume nor external cardiac work (the integral of pressure times flow during ejection) has been considered an important correlate of myocardial oxygen consumption. An initial set of experiments re-examined this question of independently varying heart rate, systolic blood pressure, and stroke volume in seven closed-chest, anesthetized dogs. This was achieved by cardiac pacing, a pressure control reservoir, phenylephrine infusion, and adjustment of arteriovenous shunts. Propranolol was used to minimize changes in contractility which might affect myocardial oxygen consumption. Stroke volume in the form of external work had a significant effect on oxygen consumption. From these results, a new pressure-work index of myocardial oxygen consumption was devised, and fitting parameters for the following indexes were determined: systolic pressure-rate product, estimated wall tension, external left ventricular work, triple product, mean pressure-rate product, Et (Bretschneider), and tension-time index. These indexes were prospectively applied to a second set of experiments in 11 closed-chest, anesthetized dogs given norepinephrine, isoproterenol, dobutamine, Nembutal, and propranolol to alter myocardial contractility. Inotropic oxygen wasting was observed with the tension-time, mean pressure-rate, triple product, and estimated wall tension indexes, but not with the pressure-work or systolic pressure-rate indexes. It is concluded that stroke work is an important correlate of myocardial oxygen consumption, and that the pressure-work of systolic pressure-rate indexes can account for catecholamine-induced, changes in myocardial oxygen consumption without postulating an oxygen-wasting effect.
Non-hydrostatic pulmonary edema after coronary artery ligation in dogs. Protective effect of indomethacin.
Authors: Richeson J F , Paulshock C , Yun P N
Published: June 2012

Pulmonary edema which develops during acute myocardial infarction is generally believed to result solely from pulmonary microvascular hypertension. However, patient with myocardial infarction and pulmonary edema occasionally are found to have normal pulmonary wedge pressure. We report data indicating that pulmonary edema develops after coronary artery ligation despite stable microvascular pressure. Four groups of open-chest dogs were studied: (1) nine dogs with left anterior descending coronary artery ligation, (2) seven dogs with sham coronary ligation, (3) seven dogs ligated after beginning an infusion of indomethacin (5 mg/kg per hr), and (4) five dogs ligated after an infusion of the drug's vehicle was begun. Extravascular lung water and pulmonary blood volume were measured at hourly intervals during the 2 hours before and after coronary ligation or sham ligation. Gravimetric lung water was measured immediately thereafter. Changes of net pulmonary intravascular driving force (the difference of microvascular hydrostatic and oncotic pressure) after ligation or sham ligation were small and comparable in all groups. Pulmonary blood volume did not change in any group. Pulmonary extravascular water volume remained constant in the sham group but rose significantly in the ligated group. Gravimetric lung water also was significantly higher in the latter group. We interpret these results to indicate that factors other than microvascular pressure can mediate the formation of these results to indicated that factors other than microvascular pressure can mediate the formation of edema during acute myocardial infarction; increased pulmonary microvascular permeability may be responsible. Indomethacin infusion blocked the formation of edema after coronary ligation, even though net microvascular driving force was highest in this group. Infusion of the vehicle alone did not prevent edema. The mechanism by which indomethacin exerts this protective effect is unclear but is probably a result of its inhibition of cyclo-oxygenase or cyclic nucleotide phosphodiesterase.
Vascular smooth muscle. Calmodulin and cyclic AMP-dependent protein kinase after calcium sensitivity in porcine carotid skinned fibers.
Authors: Rüegg J C , Paul R J
Published: June 2012

Recent work on vascular smooth muscle actomyosin has indicated that the Ca2+ sensitivity of both ATPase and superprecipitation are affected by calmodulin (CaM) and cyclic AMP-dependent protein kinase (cPK). Using a "chemically skinned" arterial preparation, we have extended these observations to the intact structured contractile system. Media from hog carotid artery were skinned with 1% Triton X-100 followed by a 50% glycerol-ATP salt solution, in which the strips were stored at -25 degrees C. Small strips (thickness between 0.1 and 0.2 mm) were mounted isometrically and relaxed in a Mg-ATP salt solution, pH 6.7, Ca2+ 10(-8) M, 30 degrees C. Ca2+ elicited a contraction with an ED50 of 10(-6) M. Isometric force was between 1 and 4 mN, consistent with the force observed before skinning. With time, the preparation became less sensitive with an increase in ED50 to 10(-5.7) M. CaM (4 micro M) reverses this loss, stabilizes the preparation, and sharply accelerates the rate of tension development. The ED50 in the presence of 4 micro M CaM shifts to about 10(-7) M. This effect is dose-dependent, with the half maximal effect at about 0.4 micro M CaM. Submaximal Ca2+ contractions can be reversibly depressed by preincubation of relaxed fibers with cPK catalytic subunit (300 U/ml), even in the presence of 4 micro M CaM. An inhibition of about 50% of the contraction at 0.2 micro M Ca2+ was obtained, whereas only 20% inhibition was found at 6 micro M Ca2+. Our findings suggest that changes in vascular contractility cannot be described solely in terms of changes in cytoplasmic Ca2+, and that changes in the sensitivity of the contractile protein to a given Ca2+ concentration are also potential mechanisms for vasodilation.
Effects of changes in extracellular ionic concentrations on aortic baroreceptors with nonmyelinated afferent fibers.
Authors: Thoren P , Andresen M C , Brown A M
Published: June 2012

The effects of ionic change upon one of the two classes of aortic baroreceptors, those having unmyelinated axons or C-fibers, have not been examined heretofore. Differences from results in aortic baroreceptors with myelinated axons might be expected because of differences in accessible surface area-volume relationships. Recordings were obtained using an in vitro aortic arch-aortic nerve preparation from 21 aortic C-fibers in 15 normotensive Wistar-Kyoto rats (WKR) 13-17 weeks old. During a slow pressure ramp, the endings responded with an irregular discharge. However, if the discharge was averaged over 10-20 seconds, the average discharge correlated well with the pressure level in the arch. The maximal discharge increased with faster ramp rates but the threshold was not shifted over the range of ramp rates employed. The relationship between pressure and discharge was tested during alterations in the extracellular concentrations of Na, K, and Ca ([Na]0, [K]0, and [Ca]0). A 12% decrease in [Na]0 clearly decreased the firing in the aortic C-fibers during a ramp stimulus. During a pressure step, the initial discharge was not decreased but the steady state discharge was clearly depressed. When the aortic arch was perfused continuously at constant pressure, a decrease in Na of only 6% depressed the activity. Doubling [K]0 increased firing for a few minutes and was followed by a reduction of discharge. Previous reports have shown no effect on myelinated baroreceptor discharge by a 12% decrease in [Na]0, a change which significantly depressed firing in all C-fiber baroreceptors in this study. Thus, C-fiber baroreceptors are more sensitive to changes in extracellular ionic composition than are baroreceptors with myelinated axons.
Uptake and tissue content of fatty acids in dog myocardium under normoxic and ischemic conditions.
Authors: van der Vusse G J , Roemen T H , Prinzen F W , Coumans W A , Reneman R S
Published: June 2012

The effect of ischemia on the myocardial content of nonesterified fatty acids (NEFA), triacylglycerol, cholesteryl esters, and phospholipids assayed with gas-liquid chromatography was studied in an open-chest dog preparation. Ischemia was induced by partial occlusion of the left interventricular coronary artery during 120 minutes (n = 20). Tissue content of the lipid classes was assessed in biopsies taken from ischemic and normoxic areas of the left ventricular free wall. Local venous blood from the concomitant vein of the left interventricular coronary artery was collected to determine myocardial extraction of lipids. In eight other dogs, no ischemia was induced (control group). Under normoxic conditions, NEFA appeared to be present in trace amounts: about 25 nmol/g wet weight of tissue, representing less than 0.1% of total myocardial fatty acids. During ischemia, NEFA increased in the affected area. This accumulation was most pronounced in the least perfused layer: the subendocardium (up to 172 nmol/g). Blood flow, estimated with radioactively labeled microspheres fell from 0.55 to 0.06 ml/min per g in this particular layer. The uptake of NEFA by the ischemic myocardium was decreased, indicating that enhanced lipolysis of endogenous lipids or reduced combustion may be held responsible for the accumulation of NEFA in ischemic tissue. Since arachidonic and linoleic acids showed the highest relative increase, lipolysis of endogenous phospholipids, rich in these fatty acids, seems to be reasonable. Ischemia had no significant effect on the content of triacylglycerol and cholesteryl esters. Phospholipids tended to decrease in the affected subendocardial layers.
Hormone receptors of the baboon cardiovascular system. Biochemical characterization of aortic and myocardial cytoplasmic progesterone receptors.
Authors: Lin A L , McGill H C , Shain S A
Published: June 2012

We used the synthetic progestin R5020 (17 alpha, 21-dimethyl-19-norpregna-4,9-diene-3,20-dione) to characterize cytoplasmic progesterone receptors in baboon (Papio sp.) aorta and myocardium. The relative ability of selected steroids to inhibit binding of radiolabeled R5020 to aortic cytoplasmic progesterone receptors was radioinert R5020, 1.0; progesterone, 0.31; triamcinolone acetonide, 0.06; testosterone, 0.002; estradiol-17 beta, 0.01; and cortisol. 0.001. The relative ability of these same steroids to inhibit binding of radiolabeled R5020 to myocardial cytoplasmic progesterone receptors was, respectively, 1.0, 0.58, 0.21, 0.01, 0.01, and 0.001. Both aortic and myocardial cytoplasmic progesterone receptors migrated as macromolecules with a sedimentation coefficient of 8-9S on low ionic strength linear sucrose gradients. Cytoplasmic binding of R5020 was inactivated by incubation of 37 degrees C. Saturation analysis at 2 degrees C showed aorta and myocardium, respectively, contained 41.6 +/- 16.1 (mean +/- SD) and was 14.0 +/- 2.8 fmol R5020 binding sites/mg cytosol protein. The dissociation constant for R5020 was 2.8 +/- 1.2 nM, aorta, and 2.0 +/- 1.1 nM, myocardium. The presence of progesterone receptors in baboon cardiovascular tissues suggests that progestins may directly influence cardiovascular tissue function.
Increase in intracellular sodium ion activity during stimulation in mammalian cardiac muscle.
Authors: Cohen C J , Fozzard H A , Sheu S S
Published: June 2012

Changes in stimulation rate alter the electrical and mechanical characteristics of myocardial cells. We have investigated the possibility that intracellular sodium activity (aiNa) changes with stimulation and correlates with changes in contraction strength. Two kinds of liquid membrane Na+-selective microelectrodes were used to measure aiNa in guinea pig and sheep ventricular muscle and in sheep Purkinje strands. Stimulation produced a rate- and time-dependent elevation of aiNa. Small increases in aiNa were seen at stimulation rates as slow as 0.2 Hz, and faster rates of stimulation elevated aiNa by over 30%. The changes seen in Purkinje strands and ventricular muscle were similar. Following a period of stimulation, aiNa and Vm returned to their pre-stimulus levels with the same time courses. This is consistent with the suggestion that the post-stimulation hyperpolarization is the result of an increased rate of electrogenic Na+ extrusion. The effects of stimulation on aiNa and tension were compared with those of ouabain. The comparison suggests that rapid stimulation could produce increased contraction strength as the result of a substantial gain in intracellular calcium via a Na-Ca exchange mechanism, but that this is only one of several factors determining the force-frequency relationship.
Energy cost of membrane depolarization in hog carotid artery.
Authors: Peterson J W , Glück E
Published: June 2012

Past studies have shown that during stable stepwise activations of vascular smooth muscle with varying concentrations of high-K+, both cytoplasmic free-Ca++ and membrane depolarization vary. On the other hand, during stepwise activations with varying concentrations of external Ca++ in the presence of constant external Ca++ in the presence of constant external depolarizing high-K+, cytoplasmic free-Ca++ varies, while membrane depolarization remains relatively constant. In this study, the rates at which suprabasal energy metabolism (oxygen consumption and lactic acid production) increased with increasing isometric tension maintenance were measured under both circumstances. Suprabasal energy metabolism with increasing membrane depolarization (increasing external K+) exceeded that with constant depolarizing-[K+] and varying Ca++ by less than 2.5% at all levels of activation, which was not statistically significant (P greater than 0.70). We conclude therefore that the steady state metabolic energy cost of membrane depolarization per se during contractile activity in vascular smooth muscle from a tonic conducting vessel (hog carotid artery) is negligible. Although the possibility cannot be excluded, we find no metabolic evidence that increased cytoplasmic free-Ca++ itself activates an ATPase associated with Ca++ sequestration and/or extrusion beyond that present in the relaxed state. Activation of hog carotid artery with an isosmotic K+-for-Na+-substituted medium fails to stimulate aerobic glycolysis at all levels of K+ substitution. Experiments were performed at the muscle length optimal for isometric tension generation and at 37 degrees C.
Altered myosin isozyme patterns from pressure-overloaded and thyrotoxic hypertrophied rabbit hearts.
Authors: Litten R Z , Martin B J , Low R B , Alpert N R
Published: June 2012

Cardiac hypertrophy, induced by pressure overload, leads to a depression in the rate of force development, velocity of shortening, tension-dependent heat generation, and myosin ATPase activity, whereas cardiac hypertrophy, induced by thyroxine administration, leads to an increase in these parameters. These changes have been attributed, in part, to structural changes in myosin. In this study, we have investigated changes in the relative content of myosin isozymes and differences in primary structure of the isozymes in pressure-overloaded and thyrotoxic cardiac hypertrophy in the rabbit. Three myosin isozymic forms (V1 = fastest, V2 = intermediate, V3 = slowest mobility) were observed in pyrophosphate polyacrylamide gels from normal hearts with the V3 component being the predominant species. In the pressure-overloaded model, the V1 and V2 components disappeared or were present in reduced amounts leaving the V3 more predominant. The most striking difference was the isozymic profile produced in thyrotoxic hearts where the V1 became the predominant component and V2 and V3 the minor components. alpha-Chymotryptic digestion of myosin heavy chains produced characteristic, reproducible peptide patterns for each of the animal models, as did fluorographic analyses of alpha-chymotryptic digests of 14C-iodoacetamide (IAA)-labeled SH1 peptides of myosin. Our results suggest that altered proportions of myosin isozymes may be responsible for altered cardiac performance.
Cholinergic mechanism in the large cat cerebral artery.
Authors: Lee T J
Published: June 2012

The isolated cat cerebral arteries (basilar, middle cerebral, anterior cerebral, and internal carotid) were studied in vitro. ACh at low concentration (3 x 10(-8) to 3 x 10(-6) M) induced relaxation, and at high concentration (10(-5) to 3 x 10(-3) M) induced constriction of the arteries with endothelial cells. In contrast, concentration of any magnitude (10(-6) to 3 x 10(-3) M) induced constriction exclusively in arteries without endothelium. Atropine (3 x 10(-6) to 3 x 10(-5) M) blocked and physostigmine (3 x 10(-6) M) potentiated both ACh-induced relaxation and constriction. These results suggest that the relaxation induced by exogenous ACh is solely dependent on the endothelial cells and that the primary effect of the direct action of ACh on the smooth muscle cells is constriction. Transmural nerve stimulation (TNS) induced a frequency-dependent relaxation in the arteries with or without endothelium. Neither atropine nor physostigmine affected the TNS-induced dilator response in either preparation. This, together with the wide separation between the nerve and endothelium in the vessel wall, suggests that ACh is not involved in TNS-induced vasodilation. Furthermore, the TNS-induced relaxation at any frequency is not smaller but greater in the arteries without endothelial cells than in those with endothelial cells. Blockade of the TNS-induced vasodilation by tetrodotoxin (TTX) or cold storage denervation did not prevent the arteries from relaxing in response to ACh or methacholine (MCh). It is suggested that the TNS-induced vasodilation is independent of the endothelial cells and that the vasodilation is due to the direct action of a yet-to-be identified dilator transmitter on the smooth muscle cells. Results of the present study support our previous finding that, in the cat cerebral artery. ACh is more likely to be a constrictor transmitter than a dilator transmitter.
The force-velocity relation and stepwise shortening in cardiac muscle.
Authors: Vassallo D V , Pollack G H
Published: June 2012

A series of experiments was carried out to determine the effects of load variation on the character of stepwise shortening. We imposed afterloaded isotonic contractions on rat ventricular trabeculae, and measured the effect of load on pause duration, i.e., on the duration of the periods during which there was no sarcomere shortening. Sarcomere lengths were measured by optical diffraction. Increases of load brought about increases of pause duration; the relation was linear. The relation did not appear to depend on time during contraction, but did depend on sarcomere length: for a given load, pauses were longer at shorter sarcomere lengths. In a supplementary protocol in which we measured the dynamics of the central segment of the muscle during muscle isometric contraction, we found that the velocity of sarcomere shortening during the shortening step was approximately independent of load. These results provide a framework for interpretation of muscle force-velocity relations: diminished velocity at high load may be the result of increased pause durations.
The role of calcium in overdrive suppression of canine cardiac Purkinje fibers.
Authors: Musso E , Vassalle M
Published: June 2012

The role of calcium in the electrical and mechanical changes induced by overdrive was studied in canine cardiac Purkinje fibers. The following results were obtained: (1) hyperpolarization and pause induced by a "short" (1-minute) overdrive are smaller in a low and larger in a high calcium solution; (2) overdriving at a constant ratio of overdrive to spontaneous rate only reduces the difference in pause duration in different calcium concentrations; (3) after overdrive, the initial diastolic depolarization is flatter and the late diastolic depolarization is steeper the control in low calcium and the opposite changes occur in high calcium; (4) the threshold for the first beat after overdrive is more negative in low than high calcium; (5) with "long" (2-minute or more) overdrives, hyperpolarization of comparable magnitude is seen during overdrive in low and high calcium; (6) the decline of hyperpolarization after overdrive is faster in high calcium unless the fiber is driven at slow rate ("postdrive"); (7) the contractile force after overdrive is greater than before overdrive in low and normal calcium and smaller than before overdrive in high calcium, and this difference is less during postdrive; (8) hyperpolarization and pause are reduced in a low sodium solution. It is concluded that calcium modifies overdrive suppression in several respects (hyperpolarization, slope of diastolic depolarization, duration of the pause and threshold), but is only one of the several factors involved in determining overdrive hyperpolarization and suppression.
Reversible alterations in excitation-contraction coupling during myocardial hypertrophy in rat papillary muscle.
Authors: Capasso J M , Aronson R S , Sonnenblick E H
Published: June 2012

To investigate the possible role of an alteration in excitation-contraction coupling in cardiac hypertrophy, we compared simultaneously recorded action potentials along with isometric or isotonic contractions of normal and hypertrophied papillary muscles. Hypertrophy was produced by renal hypertension in rats. Hypertrophied papillary muscles were taken from rats that had been hypertensive for 10 [HBP (10)] or 20 [HBP (20)] weeks. Regression of changes induced by hypertrophy was studied in rats that had been hypertensive for 10 weeks and then made normotensive for 10 weeks by removal of the ischemic kidney. Papillary muscles from age-matched, sham-operated rats [SHAM (10), SHAM (20)] were used as controls. We found that HBP (10) rats had significantly longer action potentials than SHAM (10) rats and that difference in the action potential duration recorded during isotonic and isometric contractions was significantly different from SHAM (10) and HBP (10) rats. Peak developed tension was the same in HBP (10) and SHAM (10) muscles, but the duration of isometric contraction and time-to-peak shortening were longer in HBP (10) muscles. Similarly, whereas the peak tension was the same in HBP (20) and SHAM (20) muscles, the duration of the action potential and isometric contraction, as well as the time-to-peak tension, was longer in HBP (20) muscles. The longer values for action potential duration, isometric contraction, and time-to-peak tension in HBP (20) muscles returned to SHAM values in HBP (R) muscles. The functional relationship between contraction and the action potential time course was assessed by plotting action potential duration against four parameters of contraction: peak developed tension, time-to-peak tension, time-to-half relaxation, and time-to-peak shortening. Statistical analysis of these data showed a significant correlation between action potential duration and all four parameters of contraction in SHAM (10) and SHAM (20) muscles. In contrast, HBP (10) muscles showed a significant correlation between action potential duration and only two contractile parameters, whereas action potential duration did not correlate significantly with any of the contractile parameters in HBP (20) muscles. Remarkably, in HBP (R) preparations a significant correlation was restored between action potential duration and three of the four contractile parameters. The results of this study suggest that reversible cardiac hypertrophy is associated with reversible alterations in excitation-contraction coupling. The reversibility of the mechanical and electrical alterations that accompany hypertrophy suggests, in turn, that cardiac hypertrophy is an adaptive process.
Transmural right ventricular blood flow during acute pulmonary artery hypertension in the sedated dog. Evidence for subendocardial ischemia despite residual vasodilator reserve.
Authors: Gold F L , Bache R J
Published: June 2012

Right ventricular failure during acute pressure overload has been attributed to ischemia which occurs when maximal coronary vasodilation is achieved so that further increases in myocardial blood flow cannot occur. To test the hypothesis that coronary vasodilator reserve is exhausted during acute right ventricular pressure overload, right and left ventricular myocardial blood flow was measured in 14 awake dogs during progressive pulmonary artery occlusion; coronary vasodilator reserve was tested by infusion of adenosine (4 microM/kg per min) before and during pulmonary artery occlusion. Right ventricular myocardial blood flow rose from 0.77 +/- 0.09 ml/min per g (mean +/- SEM) during control conditions to 1.69 +/- 0.27 ml/min per g during moderate pulmonary artery occlusion (P less than 0.01). With further pulmonary artery occlusion to cause increased right ventricular end-diastolic pressure and decreased aortic pressure, a selective decrease in myocardial blood flow to the right ventricular subendocardium was observed, and the right ventricular subendocardial-to-subepicardial blood flow ratio fell from 1.36 +/- 0.14 to 0.77 +/- 0.06 (P less than 0.05). With restoration of mean aortic pressure to control levels, right ventricular systolic pressure increased, right ventricular end-diastolic pressure decreased, and the right ventricular subendocardial-to-subepicardial ratio increased to 1.36 +/- 0.18 (P less than 0.01). Adenosine infusion during pulmonary artery occlusion in five dogs caused an increase in mean right ventricular blood flow (1.11 +/- 0.10 to 2.25 +/- 0.30; P less than 0.05). This increase was most marked in the outer layers but, nevertheless, was also significant in the subendocardium. These data indicate that acute severe right ventricular pressure overload may be associated with right ventricular subendocardial hypoperfusion, even when coronary vasodilator reserve is not exhausted.
Rapid resetting of low pressure vagal receptors in the superior vena cava of the rat.
Authors: Mifflin S W , Kunze D L
Published: June 2012

The discharge characteristics of mechanoreceptors located in the left superior vena cava were determined in an in vitro preparation developed from the rat. Two classes of receptors with afferent fibers in the vagus were identified on the basis of their response to steps of pressure. Slowly adapting receptors (n = 18) discharged as long as pressure was above threshold and exhibited a biphasic decline in discharge frequency in response to a pressure step. There was a rapid, initial decline in discharge frequency, complete within 15 seconds, followed by a slow, gradual decline complete within 5 minutes. Rapidly adapting receptors (n = 15) discharged irregularly or ceased firing after 5-10 seconds of a step increase in pressure. Following a 15-minute increase in perfusion pressure from 0 to 5 mm Hg, the threshold pressure of the slowly adapting receptors was increased and maximal discharge frequency and slope were decreased, whereas, in the rapidly adapting receptors, the threshold pressure was increased but maximal discharge frequency and slope were unchanged. Additional perfusion of the vessel at 5 mm Hg for up to 60 minutes produced no further increase in the degree of resetting. The resetting was reversible with discharge returning to control levels after a 15- to 25-minute return to 0 mm Hg. To determine whether the resetting of discharge following the acute pressure increase reflected a change within the receptor or an alteration of the vessel wall due to sustained distension, we examined the passive mechanical properties of the superior vena cava. Pressure-radius relationships were determined with an ocular micrometer. A 15-minute increase in pressure had no significant effect upon the mechanical properties of the vessel. Rapid resetting in these low pressure mechanoreceptors occurs with no discernible alteration in the vessel wall.
Potential fields generated by oblique dipole layers modeling excitation wavefronts in the anisotropic myocardium. Comparison with potential fields elicited by paced dog hearts in a volume conductor.
Authors: Colli-Franzone P , Guerri L , Viganotti C , Macchi E , Baruffi S , Spaggiari S , Taccardi B
Published: June 2012

The potential distribution in a homogeneous, cylindrical volume conductor surrounding an isolated paced dog heart was first measured and then calculated by using a mathematical model that stimulates an anisotropic excitation wavefront spreading through the heart muscle. The study was performed with a view to establish to what extent the anisotropy of cardiac generators affects the potential field in the extra-cardiac conducting media at a great distance from the heart. The model considers an oblique dipole layer on the wavefront which, assuming axial symmetry of the electrical properties of the fibers, can be viewed as the superposition of an axial and transverse dipole layer. These layers are, respectively, parallel and perpendicular to the local fiber due to such an oblique distribution is also equivalent to the sum of the potentials generated, respectively, by a normal and an axial dipole layer. In this form, the model generalizes the classical, uniform double layer model, upon which the solid angle theory is based, by adding to it an axial component. The features of the measured potential fields, which could not be interpreted on the basis of the solid angle theory, were satisfactorily reproduced by the model, at least on a qualitative basis. The results clearly showed the dominant role played by the axial component of the potential field even at a considerable distance from the heart.
Cellular calcium turnover in the perfused rat heart: modulation by caffeine and procaine.
Authors: Hunter D R , Haworth R A , Berkoff H A
Published: June 2012

Pool A is a rapidly exchangeable cellular pool of Ca++ whose release is triggered by a mechanism involving extracellular Ca++ (Hunter et al., 1981). We have now found that pool A is rapidly released from the perfused rat heart when 10 mm caffeine is added to the perfusate. Pool A release by caffeine was demonstrated during a Ca++ free perfusion. When the perfusate contained 2.5 mm Ca++, caffeine induced an immediate contractile failure. The steady state level of pool A (normally 69 +/- 10 nmol Ca++/g wet wt heart) was also decreased by 60%. Pool A was similarly depleted in hearts perfused with medium containing 0.2 mm Ca++. Procaine (5 mm) inhibited by 50% the release of pool A triggered by caffeine and inhibited by 86% the release triggered by extracellular Ca++. The inhibition of Ca++-induced release of pool A by procaine was partially relieved by externally stimulating the hearts. External stimulation also decreased the inhibition by procaine of Ca++ uptake by pool A from 83% to 28%. These results are further evidence that pool A is located in the sarcoplasmic reticulum and that release of pool A to the myofibriles is triggered by excitation-dependent Ca++ influx.
Heterogeneous behavior of the canine arterial and venous wall. Importance of the endothelium.
Authors: De Mey J G , Vanhoutte P M
Published: June 2012

Experiments were designed to determine the contribution of endothelial cells to the heterogeneous behavior of the arterial and venous wall. Rings of canine femoral, pulmonary, saphenous, and splenic arteries and veins, with and without endothelium, were mounted for isometric tension recording in Krebs-Ringer bicarbonate solution. Endothelium-dependent inhibitory responses to acetylcholine, adenosine triphosphate, bovine thrombin, and arachidonic acid were prominent in the arteries. In the veins, only transient endothelium-dependent relaxations to these substances were observed. Removal of the endothelium decreased the augmentation of the response to norepinephrine caused by anoxia in both arteries and veins. In the veins, arachidonic acid and thrombin caused endothelium-dependent increases in tension during contractions evoked by norepinephrine. The endothelium-independent inhibitory effects of isoproterenol and adenosine and the excitatory effects of acetylcholine and ATP were more pronounced in the veins than in the arteries. These experiments demonstrate that in the arterial and venous wall the endothelial cells can contribute to both inhibitory and excitatory responses of the smooth muscle cells of the media. Inhibitory endothelial responses prevail in the arteries, and excitatory ones in the veins.
Responses to inflation of vagal afferents with endings in the lung of dogs.
Authors: Kaufman M P , Iwamoto G A , Ashton J H , Cassidy S S
Published: June 2012

In dogs, inflating the lungs to pressures of 9 cm H2O or less reflexly increases heart rate, whereas inflating the lungs to pressures of 10-30 cm H2O reflexly decreases heart rate. The afferent fibers responsible for the cardioacceleration travel in the vagus nerves and are believed to be pulmonary stretch receptors, whereas the afferent responsible for the deceleration also travel in the vagus nerves, but are believed to be lung C-fibers. To identify the afferents responsible for these effects, we recorded the impulse activity of vagal afferents with endings in the left lung, while we slowly inflated that lung to 30-45 cm H2O. We found that 12 slowly adapting receptors fired at significantly lower inflation pressures than did 10 rapidly adapting receptors (5.8 +/- 1.5 vs. 13.5 +/- 2.2 cm H2O, respectively). We also found that 13 pulmonary C-fibers fired at significantly lower inflation pressures than did 10 bronchial C-fibers (16.4 +/- 1.8 vs 26.5 %/- 2.9 cm H2O, respectively). We conclude that slowly adapting receptors are likely to be responsible for the cardioacceleration evoked by low levels of inflation, and that both pulmonary and bronchial C-fibers are likely to be responsible for the cardiodeceleration evoked by high levels of inflation.
Ca++ distribution after Na+ pump inhibition in cultured neonatal rat myocardial cells.
Authors: Burt J M , Langer G A
Published: June 2012

The influence of inhibition of the Na+ pump, with secondary stimulation of Na+-Ca++ exchange, on cellular Ca++ distribution is examined using the on-line scintillation disk technique and cultured neonatal rat myocardial cells. Under control conditions, La+++ displaced 78.1 +/- 1.13% (SEM) of the total cell associated 45Ca. Application of 1 mm ouabain or reduction of [K+]o to 0.5 mM resulted in a net increase of 10.6 +/- 1.3% and 13.8 +/- 2%, respectively, in total cell-associated Ca++. Of this added 45Ca, 75.9 +/- 2.7% and 78.4 +/- 2.1%, respectively remained La+++-displaceable. The 45Ca-binding characteristics of isolated sarcolemma, prepared from the cultured neonatal rat myocardial cells using the gas dissection technique, were examined. When treated with either ouabain or low [K+]o solutions, sarcolemmal 45Ca binding did not change. This result indicates that functional, intact tissue is necessary to observe the Ca++ increase. Treatment of the cells with verapamil before and during ouabain exposure failed to inhibit the ouabain-induced increase in cell-associated 45Ca. The evidence indicates that inhibition of the Na+-pump, and secondary stimulation of Na+-Ca++ exchange, result in a net increase of 11-15% in cell-associated Ca++, 78% of which remains La+++-displaceable and is, therefore, localized to the sarcolemma-glycocalyx complex.
Carotid sinus baroreceptor reflex control of respiration.
Authors: Brunner M J , Sussman M S , Greene A S , Kallman C H , Shoukas A A
Published: June 2012

We have studied the effect of the carotid sinus baroreceptor reflex on respiration in 10 vagotomized, spontaneously breathing, pentobarbital anesthetized dogs. The carotid body chemoreceptor reflex response was eliminated by surgically excluding the carotid bodies from the carotid sinus baroreceptor area. Steady state frequency, tidal volume, and minute ventilation were measured after 25 mm Hg step changes in intrasinus pressure between 50 and 200 mm Hg. Over this range, the step decreases in intrasinus pressure caused concomitant increases in mean arterial pressure from 86 to 182 mm Hg. All of the respiratory response curves were sigmoidal in shape. Decreasing intrasinus pressure from 200 to 50 mm Hg caused respiratory frequency to increase from 4.8 to 9.7/min, and tidal volume to decrease from 704 to 515 ml. The calculated total ventilation, however, increased from 3180 to 4530 ml/min. The time of inspiration decreased from 3.7 to 2.4 seconds, and the time of expiration decreased from 9.8 to 4.1 seconds. These ventilatory responses are shown to be baroreceptor reflex mediated, and not secondary to changes in arterial pressure. These findings indicate that not only does the carotid sinus baroreceptor reflex control arterial pressure, but it also simultaneously influences ventilation, through changes in both respiratory frequency and tidal volume.
Amantadine-induced diastolic depolarization and automaticity in ventricular muscle.
Authors: Salata J J , Jalife J , Megna J L , Alperovich G
Published: June 2012

We studied the cardiac effects of amantadine, an antiviral and anti-Parkinson drug. Amantadine hydrochloride (100--800 microM) produced significant changes in the electrophysiological properties of isolated ventricular muscle preparations from frog, rabbit, cat, dog, and calf. At relatively low concentrations (100--300 microM), the drug increased action potential duration, decreased action potential amplitude and maximum diastolic potential, and induced phase 4 depolarization. Amantadine also caused subthreshold diastolic depolarizations, apparent upon cessation of stimulation in all preparations studied. The amplitude of the diastolic depolarizations increased as a function of time and/or concentration of drug, eventually reached threshold, and spontaneous activity ensued. In the steady state, amantadine-induced spontaneous activity was rather stable, and the rate was dependent upon the amantadine and external potassium concentrations, as well as the membrane potential. In the absence of stimulation, amantadine-induced spontaneous activity occurred abruptly or could be triggered by a single stimulus, often occurring in a "bursting" fashion that appeared to originate from multiple discrete foci. All actions of amantadine were rapidly reversed upon washout. Propranolol had no effect on the actions of the drug. Amantadine-induced spontaneous activity was unaffected by lidocaine, diminished by TTX, and reduced or abolished by verapamil. The results indicate that amantadine can directly alter the membrane properties of ventricular muscle, possibly due to an effect on potassium conductance. Furthermore, amantadine can be used as a tool to study the ionic basis of ventricular automaticity and to model cellular mechanisms of ventricular rhythm disturbances.
Myocyte hypertrophy in neonatal rat heart cultures and its regulation by serum and by catecholamines.
Authors: Simpson P , McGrath A , Savion S
Published: June 2012

The role of hormones and other humoral factors in the regulation of myocardial hypertrophy has been difficult to evaluate. We asked whether myocardial cell hypertrophy could be demonstrated in cultures from the day-old rat ventricle and evaluated the effect of serum concentration and catecholamines on the growth process. Two single-cell preparations were used: serum-supplemented, bromodeoxyuridine-treated cultures and serum-free cultures with transferrin and insulin. Both preparations were characterized by myocardial cell predominance (about 75--80% of total cells) and constant cell numbers. Myocardial cell size was documented by photomicroscopy and quantified by volume (microscopic diameter of suspended cells), surface area (planimetry of attached cells), and total cell protein concentration (Lowry method and cell counts). Growth was also evaluated in pure nonmyocardial cell cultures. In cultures with 5% (vol/vol) serum, myocardial cell size increased 2- to 3-fold over 11 days in culture. Final volume, surface area, and protein concentration were about 3000 micrometer3/cell, 5000 micrometer2/cell, and 1500 pg/cell, respectively. Serum had a dose-related effect on myocardial cell hypertrophy; myocardial cell size increased about 4-fold when serum concentration was increased from 0% to 5% or 10%. Cells maintained in serum-free medium with transferrin and insulin (each 10 microgram/ml) did not hypertrophy, but did remain responsive to the growth-promoting activity of serum. Chronic exposure to isoproterenol or norepinephrine (1 microM) significantly stimulated myocardial cell hypertrophy. This stimulation was dose-related, was not blocked by equimolar propranolol, was not associated with a sustained chronotropic effect, and was more pronounced in the serum-free preparation. In pure cultures of nonproliferating (bromodeoxyuridine-treated) nonmyocardial cells, cell size also increased with time in culture, but variation in serum concentration and addition of norepinephrine had no significant effect on cell size. Myocardial cell hypertrophy occurs in culture and is regulated by variations in the culture medium, including serum, with its contained hormones and growth factors, and catecholamines. The culture preparation can be used to explore the regulation of myocardial cell hypertrophy by nonhemodynamic factors.
A simulation study of the effects of torso inhomogeneities on electrocardiographic potentials, using realistic heart and torso models.
Authors: Gulrajani R M , Mailloux G E
Published: June 2012

The effects of torso inhomogeneities on electrocardiographic potentials were investigated via computer stimulation, using a 23-dipole heart model placed within a realistically shaped human torso model. The transfer coefficients relating the individual dipoles to the torso surface potentials, as well as the body surface potential maps, the vectorcardiogram, and the 12-lead electrocardiogram resulting due to normal activation of the heart model, were calculated for each of the following torso conditions: homogeneous, homogeneous + skeletal muscle layer, homogeneous + muscle layer + lungs, and homogeneous + muscle layer + lungs + intraventricular blood masses. The effects of each inhomogeneity were deduced by comparing results before and after its inclusion. For individual dipole transfer coefficients we confirm the validity of the "Brody effect," whereby the high conductivity blood masses augment radially oriented dipoles and diminish tangentially oriented ones. With regard to the vectorcardiogram , the electrocardiogram, and the body surface potential maps, the major qualitative effects were an augmentation of the head-to-foot component of the vectorcardiogram due to the lungs, and a smoothening of notches in the electrocardiogram (temporal filtering) and of isopotential contours in the body surface potential maps (spatial filtering) with a consequent loss of information, due to the blood masses, muscle layer, and, to a lesser extent, the lungs. Besides the above qualitative effects of the inhomogeneities, there were also large quantitative effects on the surface potentials, namely, magnitude increases due to the blood masses and magnitude decreases due to the muscle layer, that--if unaccounted for--could compromise the inverse solution of these potentials for the cardiac dipole sources.