bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional differences in adrenergic function within the left ventricle
Authors: Pierpont G. L. , DeMaster E. G. , Cohn J. N.
Published: December 2017

Since ischemic heart disease (IHD) is inhomogeneous, the adrenergic response of the heart to ischemia or infarction could depend on the level of adrenergic supply within specific regions of the myocardium. Therefore we quantified myocardial norepinephrine (NE) content of tissue samples from 54 different sites in the left ventricle (LV) of four normal dogs using high-pressure liquid chromatography with electrochemical detection. Up to 10-fold differences in NE content occurred within a single LV. The NE distribution followed a consistent pattern, demonstrating a gradient from apex (avg minimum value of 162 ng/g of tissue) to base (avg maximum value 844 ng/g). No epicardial-to-endocardial gradient was present. In six other dogs a similar pattern was found in myocardial uptake of radioactively labeled NE and epinephrine assessed 2 min after intravenous injection. These results suggest that areas of high tissue NE represent regions rich in adrenergic supply and high in adrenergic activity, not merely NE stored in inactive pools. Samples from a human autopsy specimen suggest that these findings can be extrapolated to humans.
Responses of SHR to combinations of chemical sympathectomy, adrenal demedullation, and training
Authors: Tipton C. M. , Sturek M. S. , Oppliger R. A. , Matthes R. D. , Overton J. M. , Edwards J. G.
Published: December 2017

The single and combined influences of exercise training, chemical sympathectomy (SYMX), and surgical adrenal demedullation (D) were examined in four separate spontaneously hypertensive rat (SHR) groups. SYMX was accomplished by subcutaneous injections of antinerve growth factor (ANGF) over a 5-day period after birth followed by 20 separate injections of guanethidine sulfate during a 27-day period. Measurements of urine, plasma, or tissue levels of catecholamines indicated that these experimental procedures were effective. The animals were exercise trained (T) for 10 wk or longer at 40-60% of their VO2max capacity, and all T groups exhibited longer run times or higher muscle cytochrome oxidase activity; however, only the SHR + T subgroup had a significantly higher VO2max value than its control (NT). Training lowered resting systolic blood pressure (SBP) in the SHR subgroup but normalization of SBP occurred only with SYMX. Interestingly, only the SYMX + T subgroup with intact adrenal glands also had lower SBP values than the NT. The SHR + T and SYMX + T subgroups but not the SYMX + D + T had less cardiac acceleration after ip injections of atropine than their controls. Heavier heart weights were observed only in the SHR + T subgroup; SYMX was associated with lighter heart weights regardless of whether the rats had been T or D. These collective findings demonstrated again the importance of the sympathetic nervous system to an exercise response, suggesting that an intact adrenal medulla was essential for SHR groups to achieve many of the adaptations associated with training.
Impairment of cardiopulmonary baroreflexes in Dahl salt-sensitive rats fed low salt
Authors: Ferrari A. , Gordon F. J. , Mark A. L.
Published: December 2017

Abnormalities in neural circulatory control contribute to salt-induced hypertension in Dahl sensitive (DS) rats. This study tested the hypothesis that there is impairment in cardiopulmonary baroreflex function in prehypertensive DS rats. The study was performed in DS and Dahl resistant (DR) rats fed low-salt diet. Arterial baroreceptors were denervated. Sympathetic activity was recorded from the splanchnic nerve during stimulation of cardiopulmonary baroreceptors with volume expansion (iv dextran). Resting mean arterial pressure averaged 93 +/- 6 (SE) in DS vs. 98 +/- 5 mmHg in DR rats. Resting left ventricular end-diastolic pressure (LVEDP) was 13.5 +/- 1.0 in/DS vs. 11.4 +/- 0.9 mmHg in DR rats. Volume expansion with the same amount of dextran caused greater increases in LVEDP in DS (+13 +/- 1 mmHg) than DR (+10 +/- 1 mmHg) but less inhibition of sympathetic activity (-40 +/- 4 vs. -50 +/- 2%) in DS compared with DR rats, respectively. Cardiopulmonary baroreflex gain calculated as percent inhibition of sympathetic activity divided by increases in LVEDP was -3.2 +/- 0.2 in DS vs. -4.9 +/- 0.6%/mmHg in DR rats. Reflex responses to dextran were abolished by vagotomy. Volume expansion also induced increases in mean arterial pressure. These were/greater in DS than DR rats (+43 +/- 4 vs. +28 +/- 5 mmHg, respectively) before vagotomy but were similar in the two groups after vagotomy. The distensibility (delta volume/delta pressure) of the left atrium was similar in DS and DR rats. We conclude that prehypertensive DS rats have impairment of the cardiopulmonary baroreflex.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertrophy without contractile dysfunction after reversal of pressure overload in the cat
Authors: Wisenbaugh T. , Allen P. , Cooper G. , O'Connor W. N. , Mezaros L. , Streter F. , Bahinski A. , Houser S. , Spann J. F.
Published: December 2017

To determine whether a causal relationship exists between the myocardial hypertrophy and the deficits in myosin ATPase activity and contractile function that have been associated with chronic, experimental pressure overload, we studied contractile function, myosin ATPase, and isomyosin pattern in a model of severe pressure overload in which the pressure overload was surgically relieved but hypertrophy persisted. Severe hypertrophy, contractile dysfunction, and pump failure were produced in the cat right ventricle by tight pulmonary arterial banding. In two groups of cats banded for 2- and 7-wk periods, right ventricular mass doubled, and contractile function was severely depressed compared with controls. In another group of cats subjected to severe right ventricular pressure overload for 4 wk, pressure overload was reversed by removal of the pulmonary arterial band. After a 4-wk recovery period for this group, right ventricular mass remained markedly increased, but contractile function had returned to normal. Changes in neither isomyosin composition nor myosin ATPase activity were found regardless of contractile function. Thus, following reversal of a right ventricular pressure overload severe enough to cause pump failure and a twofold increase in right ventricular mass, muscle contractile function can return to normal even when severe hypertrophy persists. Furthermore, changes in myosin isozyme composition or ATPase activity do not explain the changes in contractile function.
Effects of beta-blockade on regional myocardial flow and function during exercise
Authors: Matsuzaki M. , Patritti J. , Tajimi T. , Miller M. , Kemper W. S. , Ross J.
Published: December 2017

We examined the effects of a cardioselective beta-blocking drug on exercise-induced regional myocardial ischemia in 10 conscious dogs with chronic coronary artery stenosis. An ameroid constrictor, Doppler flowprobe, and hydraulic cuff were placed around the left circumflex coronary artery, and left ventricular pressure (LVP), systolic wall thickening (% delta WT; by sonomicrometry), and myocardial blood flow (MBF; microspheres) were measured during control standing, control treadmill exercise, and identical exercise after atenolol (1 mg/kg po). Prior to study, in every dog % delta WT and MBF in the ischemic area were normal at rest, indicating collateral development. During control exercise, % delta WT in the ischemic region markedly decreased from 27 to 4%, and transmural ischemia was evident in that region. Heart rate, systolic LVP, and LV (+)dP/dt were significantly lower during exercise after atenolol than during control exercise. % delta WT in the normal area was only 81% of that during control exercise, but dysfunction in the ischemic area was improved (77% increase compared with control exercise). Accompanying the improved function was a significant increase of MBF/beat and relative MBF in the ischemic zone; the endocardial-to-epicardial ratio increased from 0.27 to 0.47. Thus atenolol improved regional MBF distribution, thereby diminishing exercise-induced regional myocardial dysfunction and accelerating its recovery.
Reduction of contraction-induced arteriolar vasodilation by adenosine deaminase or theophylline
Authors: Proctor K. G.
Published: December 2017

To test the hypothesis that adenosine mediates striated muscle blood flow, the cremaster muscle microcirculation was exposed to a continuous superfusion (10-30 min) of either a control, adenosine deaminase (7 micrograms protein/ml), or theophylline (10(-5) M) solution before, during, and following twitch contraction. Small arteriolar diameter and (dual-slit) blood flow velocity were continuously measured for 3 min before and after 2 min of electrical stimulation at 10, 5, or 2 Hz. Estimated arteriolar volume flow was calculated at 10-s intervals. The peak and average arteriolar diameter, peak and average estimated volume flow, duration of the exercise evoked response, and the total estimated volume of blood delivered in the 3-min postexercise period were reduced by deaminase as a function of stimulus frequency relative to a paired control. Deaminase reduced total estimated blood flow by 44, 35, and 22% at 10, 5, and 2 Hz, respectively. Although theophylline was more damaging to the tissue at a dose that was equieffective with deaminase, it produced a consistent reduction in peak and average arteriolar diameter and estimated volume flow after 5-Hz exercise. If changes in small arteriolar diameter are proportional to tissue blood flow changes, then these observations support the hypothesis that adenosine contributes to contraction-induced hyperemia in skeletal muscle in free-flow conditions and that its regulatory contribution depends on the intensity of the metabolic stimulus. Alternatively, these data could implicate adenosine in exercise-induced capillary recruitment.
Interaction of serum proteins with lung endothelial glycocalyx: its effect on endothelial permeability
Authors: Schneeberger E. E. , Hamelin M.
Published: December 2017

To examine directly the interaction of circulating proteins (CP) with the glycocalyx of pulmonary endothelium and its effect on endothelial permeability, two types of experiments were carried out. In the first, rats were exchange transfused with graded amounts of FC-43 fluorocarbon emulsion (FCE) resulting in CP concentrations of 25, 10, and 4 mg/ml, respectively. In the second, rats were exchange transfused with FCE to remove 99.9% of CP. The rats were then exchange transfused with 1 ml FCE containing 60 mg/ml of rat serum protein and killed 3.5, 7.5, and 15 min after the administration of protein. In all animals the distribution of albumin and immunoglobulin G (IgG) was visualized by immunocytochemistry, and endothelial permeability to native ferritin was measured by morphometry. In the depletion experiments increased endothelial permeability to ferritin coincided with loss of adsorbed albumin and IgG from the glycocalyx. Conversely, the presence of administered serum proteins in the glycocalyx and in a few luminal vesicles was associated with an endothelial permeability to ferritin indistinguishable from that of controls. These observations suggest that the adsorption of CP to the endothelial glycocalyx renders the underlying endothelium less permeable to ferritin.
New Ca2+ agonist (Bay K 8644) enhances and induces cardiac slow action potentials
Authors: Wahler G. M. , Sperelakis N.
Published: December 2017

Bay K 8644 is an analogue of nifedipine that has positive inotropic and vasoconstricting actions and was postulated to be a Ca agonist (i.e., a Ca2+-channel activator). To test this hypothesis, we examined the electrophysiological effects of this compound in isolated guinea pig papillary muscles. Bay K 8644 (10(-6) M) had little effect on the normal fast action potentials, although it did increase contractility. Bay K 8644 did, however, induce Ca2+-dependent slow action potentials (fast Na+ channels inactivated by 25 mM K+). When slow action potentials had been previously induced by tetraethylammonium chloride (10 mM) plus Ca2+ (4.0 mM) or isoproterenol (2 X 10(-7) M), 10(-6) M Bay K 8644 potentiated the slow action potentials, i.e., increased their maximal rate of rise (Vmax), concomitant with its positive inotropic effect. All effects of Bay K 8644 could be reversed by 10(-6) M nifedipine. Thus it appears that Bay K 8644 enhances Ca2+ influx through the myocardial slow channels, consistent with the concept that Bay K 8644 is a Ca2+-channel stimulator.
Segmental and total microvascular resistances during hemorrhagic hypotension in rabbit omentum
Authors: Firrell J. C. , Lipowsky H. H. , Usami S. , Chien S.
Published: December 2017

Single input-output microvascular modules in the rabbit omentum were studied to quantitate total modular resistance (RT) and the changes in resistance of successive serial segments (Rseg) during hemorrhagic hypotension (55 mmHg for 1 h). RT was calculated from the pressure drop between input and output vessels and the total flow through the module. Changes in Rseg were estimated from alterations in single microvessel hindrance (1/diam4) for selected microvessels within a module together with a correction for flow redistribution within each segment derived from changes in the proportion of total flow. Mean RT increased to 2.1 times control within the first 10 min of systemic hypotension and gradually declined over 1 h. Response of Rseg varied in different generations of microvessels (arterioles and venules subdivided by size). Rseg for arterioles and venules less than 30 microns, but not that for arterioles and venules greater than 30 microns, showed comparable or greater changes than RT. Calculated differences between RT and the summed Rseg of measured segments suggest that the unmeasured Rseg in capillaries and blood rheological parameters may have significantly influenced changes in RT during hemorrhagic hypotension.
Developmental changes in cardiac contractility in fetal and postnatal sheep: in vitro and in vivo
Authors: Anderson P. A. , Glick K. L. , Manring A. , Crenshaw C.
Published: December 2017

Developmental changes in contractility were sought in the fetal and postnatal sheep heart by using postextrasystolic potentiation and force, pressure, and wall-motion measures. Two different preparations were used, isolated myocardium and the chronically instrumented lamb. In the isolated muscle, the following increased significantly with age: force of contraction, the maximum rate of rise of force, and postextrasystolic potentiation. In the intact heart prior to birth [period of study, 20 +/- 4 (SD) days] heart rate (HR) fell significantly, and the following increased significantly: postextrasystolic potentiation [measured with the maximum rate of rise of left ventricular (LV) pressure (Pmax)], LV peak systolic pressure (LVP), end-diastolic dimension (EDD), end-systolic dimension (ESD), and aortic diastolic pressure. After birth, LVP, Pmax, HR, LVEDP, EDD, and ESD increased and postextrasystolic potentiation fell. The latter fall was not found in vitro and probably demonstrates a transient change in contractility, related to hormonal or neural stimulation. Over the subsequent postnatal days (6-122 days), HR fell while potentiation, EDD, and ESD increased significantly. Both in vitro and in vivo, the overall increase in postextrasystolic potentiation demonstrates a similar long-term change in contractility. The similarity of this change to that induced by mild hypertrophy suggests that development and mild hypertrophy alter myocardial contractility through a common mechanism.
Total adenine nucleotide stores and sarcoplasmic reticular Ca transport in ischemic rat heart
Authors: Meno H. , Kanaide H. , Okada M. , Nakamura M.
Published: December 2017

We studied the relation between the contractility and metabolic changes in reperfusion after ischemia, and the effect of diltiazem on these changes, in an isolated rat heart perfused using the Langendorff method. After aerobic perfusion at 80 cmH2O, the perfusion pressure was reduced to 10 cmH2O to induce global ischemia. Substrate was removed from the perfusate during ischemia. After 30 or 60 min of ischemia, the heart was reperfused in an aerobic condition. During ischemia, the total adenine nucleotide level (TAN: sum of ATP, ADP, and AMP) was progressively reduced and the ATP-to-ADP ratio was one-third of the value obtained in an aerobic condition. With 30 min of subsequent reperfusion, ATP increased, and the shorter the duration of ischemia, the closer ATP/ADP approached the value of an aerobic condition, whereas TAN was equivalent to the value shown immediately before reperfusion. Thus the degree of ATP recovery by reperfusion mainly depends on the amount of TAN immediately before reperfusion and the mitochondrial function of oxidative phosphorylation that determines ATP/ADP. The calcium transport activity of the sarcoplasmic reticulum of myocardial cells was affected by ischemia and showed no amelioration or further deterioration by subsequent reperfusion. When diltiazem (10(-5)M) was added to the perfusate continuously from 5 min before ischemia, during ischemia, and until 10 min of reperfusion, the amount of TAN in ischemia and reperfusion and the calcium transport activity during reperfusion were maintained at relatively high levels. The degree of contractility recovery by reperfusion showed direct correlations with both the tissue ATP amount and the level of calcium transport activity in the sarcoplasmic reticulum.
Effects of reducing fatty acid metabolism on mechanical function in regionally ischemic hearts
Authors: Liedtke A. J. , Nellis S. H. , Mjos O. D.
Published: December 2017

Fatty acids in excess impair mechanical function and electrical stability in ischemic hearts. The purpose of the present studies was to test whether oxfenicine, an agent capable of reducing fatty acid metabolism, can prevent these consequences and in so doing improve hemodynamic performance. Two groups of working swine hearts (n = 15), extracorporeally perfused with whole blood, were compared over 90 min of controlled coronary perfusion. An emulsion of triacylglycerols (Intralipid) with heparin were administered systemically to augment serum fatty acids threefold (0.30 to 0.92 mumol/ml). Labeled [U14C]palmitate was administered selectively into the left anterior descending coronary circulation to follow fatty acid oxidation. Coronary flow in this bed was decreased by 50% over the final 30 min of perfusion. Saline (n = 7) or oxfenicine (17-33 mg/kg, n = 8) was administered to placebo or treated animals at 30 min perfusion. 14CO2 production from labeled palmitate was decreased by 55% (P less than 0.025) at normal flows in oxfenicine-treated hearts and was reduced further during ischemia. Tissue levels of acyl carnitine were significantly reduced and acetyl CoA levels significantly increased in oxfenicine-treated hearts both in aerobic and ischemic myocardium. These changes were associated with an improvement in mechanical function. Left ventricular systolic and developed pressures and maximum left ventricular dP/dt were increased by 36 delta %, P less than 0.01; 46 delta %, P less than 0.025; and 41 delta %, P less than 0.025, respectively, at end ischemia as compared with placebo hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of indomethacin on coronary blood flow during graded treadmill exercise in the dog
Authors: Dai X. Z. , Bache R. J.
Published: December 2017

This study tested the hypothesis that metabolites of arachidonic acid may contribute to the coronary vascular response to physiological increases of myocardial O2 consumption that occur during exercise. Studies were performed in eight chronically instrumented dogs with electromagnetic flowmeter probes on the left circumflex coronary artery and aortic and coronary sinus catheters. Data were obtained at rest and during graded treadmill exercise during control conditions and after administration of the cyclooxygenase inhibitor indomethacin. During control conditions heart rate, aortic pressure, and coronary blood flow increased progressively during exercise; this was accompanied by a significant increase in myocardial O2 extraction, as evidenced by a decrease in coronary venous O2 tension (Po2) particularly during the first stage of exercise. Indomethacin (5 mg/kg iv) resulted in marked blunting of the coronary vasodilator response to intracoronary arachidonic acid in anesthetized open-chest dogs. After administration of indomethacin to awake dogs, resting heart rate, aortic pressure, and coronary venous Po2 were unaltered, and the response of these variables to exercise was not changed. The increase in coronary blood flow during exercise was also unchanged after indomethacin, so that the relationship between myocardial O2 consumption and coronary blood flow was unaltered by cyclooxygenase inhibition. Thus we were unable to demonstrate a significant effect of the prostaglandin system in mediating the coronary vascular response to exercise.
An in situ brain perfusion technique to study cerebrovascular transport in the rat
Authors: Takasato Y. , Rapoport S. I. , Smith Q. R.
Published: December 2017

The right cerebral hemisphere of the rat was perfused in situ by retrograde infusion of HCO3 saline or blood into the right external carotid artery. Infusion rate was adjusted to minimize the contribution of systemic blood to flow in the hemisphere. During perfusion with whole or artificial blood, regional cerebral blood flow and blood volume were comparable to respective values in the conscious rat, whereas perfusion with HCO3 saline increased regional flow three- to fourfold due to the low viscosity of the saline perfusate. Perfusion with whole blood for 300 S or with HCO3 saline for 60 S did not alter the permeability of the blood-brain barrier. Cerebrovascular permeability coefficients of eight nonelectrolytes ranged from 10(-8) to 10(-4) cm X S-1 and were directly proportional to the octanol-water partition coefficient of the solute. Thus the in situ brain perfusion technique is a sensitive new method to study cerebrovascular transfer in the rat and permits absolute control of perfusate composition.
Influence of cardiac denervation on subsidiary atrial pacemaker stabilization
Authors: Sterba J. A. , Rinkema L. E. , Randall W. C. , Jones S. B. , Brynjolfsson G.
Published: December 2017

Overdrive suppression was determined by measuring cardiac cycle lengths after rapid atrial pacing in nine alert conscious dogs sustaining total intrapericardial denervation. Rapid atrial pacing was performed at 125-400% of spontaneous heart rate for 30 s and at 200% spontaneous rate for 30, 60, 120, and 180 s, with and without cholinergic (atropine 0.2 mg/kg iv) or adrenergic blockade (propranolol 0.5 mg/kg iv). Corrected recovery time (CRT) was defined as the first recovery cycle length minus average control cycle length. To compare responses of the intact sinoatrial node (SAN) and subsidiary atrial pacemakers, CRT was measured in the conscious animal before and after SAN excision. Immediately after SAN excision, a junctional rhythm was frequently observed, but within a short time (min-h), subsidiary atrial pacemaker dominance was established with well-formed P waves and P-R interval averaging 85.3 +/- 3.4 ms. CRT before SAN excision ranged from 100 to 300 ms. Following pacing at 125-400% of spontaneous heart rate soon after SAN excision, CRT was markedly prolonged, ranging up to 6,000 ms. Atropine and propranolol did not influence CRT in the denervated preparation. CRT of subsidiary atrial pacemakers in the normally innervated dog heart returned to control pre-SAN excision values in 1-2 wk. In the denervated heart complete autonomic denervation exaggerated time required for return to control CRT values to 5-8 wk.
Effects of chronic tobacco smoke exposure on arterial blood pressure regulation
Authors: Bennett C. H. , Richardson D. R.
Published: December 2017

The purpose of this study was to determine the effects of long-term consumption of tobacco smoke on arterial blood pressure regulation. Male Sprague-Dawley rats were administered tobacco smoke for 6-8 mo. Two groups of animals (A and B) received tobacco smoke containing different levels of nicotine (group A: high nicotine, 4 mg/cigarette; group B: low nicotine, 1 mg/cigarette), while a third group (C) served as a sham control by receiving only puffs of room air. Reflex adjustments in mean arterial blood pressure (MAP), heart rate (HR), lower body blood flow, and lower body vascular resistance were compared between the three groups. In the anesthetized control state, no significant difference existed for the cardiovascular parameters measured in the three groups. However, perturbating the cardiovascular system by reducing central blood volume via a 60 degrees head-up tilt elicited less of a fall in MAP in the two smoke groups compared with the sham group. Percent decreases in MAP follow: group A, 23%; group B, 22%; and group C, 48%. Increasing MAP with phenylephrine elicited a significantly greater (P less than 0.05) reduction in HR in groups A and B (smoke treated) compared with group C (sham treated). Finally, varying carotid sinus pressure elicited significantly greater (P less than 0.01) changes in MAP in the smoke-treated animals (A and B) compared with the sham group (C). It is concluded that chronic tobacco smoke administration to laboratory rats increases the sensitivity of the reflex control of the cardiovascular system.
Slow inactivation of Vmax in guinea pig ventricular myocardium
Authors: Clarkson C. W. , Matsubara T. , Hondeghem L. M.
Published: December 2017

Measurements of maximum upstroke velocity (Vmax) of guinea pig ventricular action potentials were used to investigate the effect of prolonged depolarization on the inactivation and recovery kinetics of cardiac sodium channels. Membrane potential before stimulated upstrokes was controlled by passing current across a sucrose gap. Two phases of inactivation ("slow" and "ultra-slow") having kinetics and voltage dependence different from the commonly observed fast inactivation process were observed. Ultra-slow inactivation developed exponentially with a time constant of several minutes between -60 and -20 mV. In contrast, slow inactivation developed with a time constant of 1-6 s between -60 and 40 mV. Under steady-state conditions slow and ultra-slow inactivations were virtually absent at -85 mV, while 50% of Vmax underwent slow inactivation at approximately 10 mV and 50% underwent ultra-slow inactivation at approximately -40 mV. Recovery from slow inactivation occurred exponentially with a time constant of about 2 s at -70 to -85 mV and 0.7 s at -100 mV. Recovery from ultra-slow inactivation was not completely characterized but was complete within 20 s at -85 mV. No significant effect of external [K+] (1-10 mM) on slow inactivation was found. The results suggest the existence of two additional inactivated states of the cardiac sodium channel distinctly different from the fast inactivated state.
An automated simultaneous transmural cardiac mapping system
Authors: Witkowski F. X. , Corr P. B.
Published: December 2017

The origin and propagation sequence of cardiac depolarization in situ requires accurate simultaneous three-dimensional information from multiple sites. Likewise, the mechanism underlying an arrhythmia can often be elucidated by determining the course of impulse propagation through the heart, particularly if information can be obtained from multiple sites simultaneously, allowing analysis of transient or rapidly occurring events. The most significant problem with obtaining such detailed continuous information is the large amount of data storage required as well as the need for rapid analysis. In the present system these problems are overcome by immediate conversion of all electrograms from analog to digital for all subsequent storage and processing. The bipolar electrogram information is acquired from 240 cardiac sites simultaneously at a sampling rate of 2 kHz with continuous and total data storage of up to 60 min. Rapid two-dimensional isochronic maps at multiple depths (effective 3-dimensional information) are presented via computer-generated interactive graphics. System design permits easy expansion to almost 2,000 simultaneous sites. Surgical electrophysiological intraoperative studies in humans are performed at an operating room located 2,000 ft from the computer facility with all communications carried by a fiber-optic link. The system allows both experimental and clinical cardiac mapping from multiple sites from a single cardiac depolarization, minimal redundancy of costly hardware, and direct rapid visualization of all original electrogram data.
Vascular effects of free radicals generated by electrical stimulation
Authors: Lamb F. S. , Webb R. C.
Published: December 2017

Electrical field stimulation (9 V, 1.0 ms, 4 Hz) of isolated segments of rat tail arteries and dog coronary arteries inhibits contractile responses to exogenous norepinephrine and elevated potassium concentration. This inhibitory effect of electrical stimulation is blocked by various agents that alter oxygen metabolism: superoxide dismutase, catalase, glutathione, ascorbate, and dimethyl sulfoxide. The observations suggest that the inhibitory effect is due to an action of oxygen free radical metabolites that are generated by the electrical stimulation of the oxygen-rich buffer. These free radical metabolites have two actions: 1) they oxidize drugs in the experimental system, and 2) they exert a direct inhibitory action on vascular smooth muscle.
Chronic immunosuppression attenuates hypertension in Okamoto spontaneously hypertensive rats
Authors: Khraibi A. A. , Norman R. A. , Dzielak D. J.
Published: December 2017

Recent evidence suggests that hypertension in the Okamoto spontaneously hypertensive rat (SHR) may be the result of an autoimmune disorder. To test this hypothesis SHRs were given chronic immunosuppressive therapy (cyclophosphamide). The development of spontaneous hypertension was studied in SHRs receiving cyclophosphamide beginning at age 3 wk. The arterial pressure of the cyclophosphamide-treated SHRs was significantly lower than that of untreated control SHRs once the rats were 8 wk old, and this reduction in blood pressure was maintained for the duration of treatment. Also the effect of chronic immunosuppressive therapy on the maintenance of spontaneous hypertension was determined by beginning treatment in 16-wk-old SHRs. Arterial pressure was significantly less than that of untreated control SHRs after 2 wk of treatment. According to tail-cuff measurements, the level of hypertension in the SHRs was reduced by approximately 50% following 6 wk of immunosuppressive therapy. The mean arterial pressure was significantly reduced after 6 wk to 158 +/- 5.0 mmHg in immunosuppressed SHRs (n = 10) compared with 174 +/- 2.6 mmHg in control SHRs (n = 7). Cyclophosphamide treatment did not have a significant effect on the blood pressure of Wistar or Wistar-Kyoto rats or on the development or maintenance of deoxycorticosterone acetate hypertension. Chronic immunosuppression attenuates hypertension in the Okamoto SHR. These results support the hypothesis that spontaneous hypertension may be due in part to an autoimmune disorder.
Validation of 3-deoxy-3-fluoro-D-glucose as a glucose transport analogue in rat heart
Authors: Halama J. R. , Gatley S. J. , DeGrado T. R. , Bernstein D. R. , Ng C. K. , Holden J. E.
Published: December 2017

Four aspects of the behavior of 3-deoxy-3-fluoro-D-glucose (D-3FDG) were studied. The distribution of label in rat tissues after intravenous administration of [18F]D-3FDG was compared with that seen with labeled 3-deoxy-3-fluoro-L-glucose (L-3FDG). Results were consistent with a larger volume of distribution for the physiological D-isomer coupled with some degree of reabsorption by the kidneys. L-3FDG, but not its D-isomer, was excluded from the brain. D-3FDG competitively inhibited uptake of glucose by isolated perfused rat hearts. The inhibition constant was 12.8 +/- 1.6 mM compared with 6.1 +/- 1.1 mM for 3-O-methyl-D-glucose. Residue curves obtained after bolus administration of [18F]D-3FDG to isolated hearts indicated phosphorylation of the tracer at a lower rate than for 2-deoxy-2-fluoro-D-glucose but with subsequent dephosphorylation at a faster rate. Chromatographic analysis of 18F remaining in tissues after administration of [18F]D-3FDG revealed in addition to free D-3FDG three other peaks. These disappeared after treatment with alkaline phosphatase and were thus assigned as phosphates. The principal metabolite had the same retention time as D-3FDG-6-phosphate prepared with hexokinase. No phosphorylated metabolites were detected in blood. D-3FDG labeled with 18F may be a useful tracer in studies of glucose transport and metabolism.
Filtration through damaged and undamaged rabbit thoracic aorta
Authors: Tedgui A. , Lever M. J.
Published: December 2017

The influence of luminal pressure and endothelial removal on fluid filtration across the arterial wall has been studied in the rabbit thoracic aorta. Segments of aorta were excised in such a way as to prevent shortening and depressurization and were filled with a 4% albumin-Tyrode solution. Experiments were carried out at two controlled pressure levels (70 and 180 mmHg). The hydraulic conductivity (Lp) of the total wall, calculated from the filtration data, was 4.00 +/- 1.31 and 2.44 +/- 0.80 (SD) X 10(-8) cm/(s X mmHg) in intact wall at 70 and 180 mmHg, respectively (P less than 0.01), whereas values for deendothelialized arteries were higher (P less than 0.01), being 5.36 +/- 1.62 and 5.27 +/- 0.84, respectively. The apparent pressure dependence of conductivity of the intact wall may be due to altered strain of the interstitial matrix. Removal of the endothelium can increase the hydration and porosity of the medial interstitium but, assuming that the conductivity of the deendothelialized wall at 70 mmHg is the same as that of the normal media, the calculated conductivity of the endothelium is 15.76 X 10(-8) cm/(s . mmHg).
Acute resetting of carotid sinus baroreceptors. I. Dissociation between discharge and wall changes
Authors: Heesch C. M. , Thames M. D. , Abboud F. M.
Published: December 2017

The purpose of this study was to assess whether mechanical changes in the carotid sinus wall could account for acute resetting of the carotid sinus baroreceptors in chloralose-anesthetized dogs. Threshold pressure and pressure-discharge curves for single-unit baroreceptors were determined before and after the vascularly isolated carotid sinus was exposed to brief increases or decreases in base-line pressure. When intrasinus pressure was increased by 30 mmHg for 15 min, threshold pressure increased by 9 +/- 1.3 (SE) mmHg (n = 12), and when intrasinus pressure was decreased by 30 mmHg threshold pressure decreased by 14 +/- 4.2 mmHg (n = 9), with no change in gain of the pressure-discharge curves. In 14 experiments carotid sinus pressure was increased from 70 (control) to 160 mmHg for only 5 min (reset) and returned to 70 mmHg for 10 min (recovery). After exposure to the higher pressure, threshold pressure increased from 75 +/- 3.8 to 94 +/- 4.4 mmHg, and carotid sinus diameter (sonomicrometer) and calculated wall strain at each pressure increased. After the recovery period, baroreceptor threshold pressure returned to 75 +/- 4.1 mmHg, but diameter and wall strain remained elevated. We interpret our finding that baroreceptor resetting and recovery are not accompanied by reciprocal changes in carotid sinus diameter to indicate that a mechanical mechanism alone cannot explain acute resetting.
Validation of a third-generation Doppler system for studies of detailed aortic flow
Authors: Rumberger J. A. , Fastenow C. F. , Laughlin D. L. , Marcus M. L.
Published: December 2017

A multigated, third-generation Doppler velocity system has been developed and validated for detailed studies of aortic hemodynamics. The Doppler system employs a single 3-mm, 5-MHz crystal applied to the aorta at a fixed angle with respect to the flow axis and is capable of measuring velocity profile, blood vessel diameter, and integrated volume flow on a continuous, real-time basis. This represents a major developmental advance over existing first-generation, continuous-wave and second-generation, single-gated pulsed Doppler systems. Validation studies have been performed in vitro and in dogs. Aortic diameter was measured simultaneously with the volumetric Doppler system and with sonomicrometer probes. During changes in aortic diameter between 8 and 18 mm (n = 18), produced by temporary pulmonary artery occlusion or epinephrine infusion, quantitative agreement between the Doppler and sonomicrometer probes was found (r = 0.96). Velocity profile measurements and axial velocity values made with the Doppler system compared favorably with hot-film anemometry studies in vitro and in vivo. Although the current system is nondirectional, measurements of phasic aortic volume flow and absolute-time-averaged changes in flow rates showed an excellent correlation with chronically placed electromagnetic flow probes over a broad range of flow rates in vivo (1-5 l/min, n = 36, r = 0.95). This third-generation Doppler system should prove useful in clinical and research studies of detailed aortic hemodynamics.
Tetrodotoxin-resistant relaxation to transmural nerve stimulation in isolated saphenous vein
Authors: Senaratne M. , Kappagoda T.
Published: December 2017

The response to transmural nerve stimulation (TNS) was characterized in rings of canine saphenous veins following sympathetic (guanethidine 10(-4) mol/l; phenoxybenzamine 2 X 10(-5) mol/l; propranolol 2 X 10(-6) mol/l) and muscarinic blockade (atropine 5 X 10(-6) mol/l). In preparations which were contracted with prostaglandin F2 alpha, TNS was applied as intermittent trains of stimuli of 30 s duration at frequencies of 1-32 Hz. This stimulus elicited a frequency-dependent relaxation [maximum relaxation 3.4 +/- 0.21 (SE) g]. This relaxation was present in rings denuded of endothelium and was not altered significantly by cimetidine (10(-4) mol/l), indomethacin (10(-5) mol/l), aminophylline (10(-5) mol/l),or cyproheptadine (10(-6) mol/l). It was abolished by the Na+-K+-ATPase inhibitor ouabain (2 X 10(-4) mol/l) and in zero-K+ Krebs solution. When the experiment was repeated following storage of the isolated saphenous veins for 9 days at 4 degrees C TNS failed to induce any relaxation. However, the relaxation in fresh rings was not abolished by tetrodotoxin (10(-6) mol/l). The present study demonstrates a nonadrenergic noncholinergic relaxation to TNS in the saphenous vein which could be mediated by 1) a tetrodotoxin-resistant nerve or 2) a direct effect of TNS on the smooth muscle.
Aortic bulb-aortic orifice hemodynamics in left ventricle-systemic arterial interaction
Authors: Campbell K. B. , Ringo J. A. , Klavano P. A. , Robinette J. D. , Alexander J. E.
Published: December 2017

Experiments were conducted in open-chest dogs in which ascending aortic blood flow (Q) was measured with an electromagnetic flow probe, and pressure was measured in the left ventricle (LV) and ascending aorta. The aorta just distal to the flow probe was occluded suddenly, causing the aortic bulb (AB) to be the only part of the arterial system to be in communication with the LV during clamped beats. Pressure and flow data from preocclusion, occlusion, and occlusion-release periods were analyzed to assess AB compliance (CAB) and the longitudinal impedance properties of inertance (LVO) and resistance (RVO) in the AB-aortic orifice region. In five dogs (avg wt 24.2 kg), the mean and range of values were as follows: CAB = 45 (31-55) X 10(-4) cm5/dyn; LVO = 1.86 (0.76-2.88) dyn X s2 X cm-5, RVO = 4.07 (0.66-8.55) dyn X s X cm-5. The volume-accommodating actions of CAB caused actual LV outflow to be characteristically different from Q and aortic-clamped beats to be nonisovolumic. Actions of the AB were found to be important in the estimation of arterial characteristic impedance as a component of LV afterload and in the estimation of the LV pump properties of time-varying elastance and internal resistance.
Peritoneal absorption of macromolecules studied by quantitative autoradiography
Authors: Flessner M. F. , Fenstermacher J. D. , Blasberg R. G. , Dedrick R. L.
Published: December 2017

Transport experiments of 125I-human serum albumin from the peritoneal cavity to the plasma were conducted in 200-g female rats. Blood and peritoneal samples were collected at intervals over 2-3 h. After death and rapid freezing of the animal, transverse sections were cut in a cryomicrotome from several tissues surrounding the peritoneal cavity, and the distribution of the labeled albumin was measured by computerized quantitative macroautoradiography. Tissue concentrations (counts/min per wet tissue wt) in parietal tissues (anterior abdominal wall and the diaphragm) were relatively constant versus distance from the peritoneum and represented a large fraction (0.5-1.0) of the concentration in the peritoneal cavity. Fractional concentrations in visceral tissues (liver, stomach, intestine) decreased from 0.20-0.35 at the peritoneal surface to 0.03-0.06 at a distance of 900 micron from the peritoneum. Uterine tissue concentrations lay between those of the parietal tissues and those of the viscera. The data are related to mechanisms of interstitial and lymphatic transport in these tissues.
Selective parasympathectomy of automatic and conductile tissues of the canine heart
Authors: Randall W. C. , Ardell J. L.
Published: December 2017

From right thoracotomy (T4-T5), the canine heart was suspended in its pericardium to expose its major venous inputs. Vagal and sympathetic trunks were prepared for electrical stimulation (10-20 Hz, 5.0 ms, 3-5 V) before and after each separate denervation procedure. Vagal stimulation was instituted with and without concurrent atrial pacing. The following surgical interventions were performed. 1) The superior vena cava was cleared of connective and nervous tissues from the pericardial reflection caudally to the level of the right pulmonary artery. 2) The azygos vein was cleared, tied, and sectioned. 3) The right pulmonary veins were isolated and cleared intrapericardially. 4) The dorsal surface of the atria was dissected between the right and left pulmonary veins and painted with phenol. Each step in the procedure elicited successive stepwise deletion of parasympathetic influences on sinoatrial tissues of the canine heart with only minor ablation of sympathetic inputs. 5) Dissection of the triangular fat pad at the junction of the inferior vena cava and inferior left atrium eliminated the remaining parasympathetic efferent input to the heart with dramatic deletion of atrioventricular block during either left or right vagal stimulation, again with preservation of most of the sympathetic innervation. These experiments clearly demonstrate differential and selective inputs of parasympathetic pathways to sinoatrial (SAN) and atrioventricular (AVN) regions of the dog heart but relatively little interference with sympathetic distributions.(ABSTRACT TRUNCATED AT 250 WORDS)
Correlation between cardiac performance and plasma catecholamine levels in conscious dogs
Authors: Young M. A. , Hintze T. H. , Vatner S. F.
Published: December 2017

We correlated levels of circulating norepinephrine (NE) and epinephrine (Epi) induced by 1) infusions, 2) treadmill exercise, and 3) hemorrhage with left ventricular (LV) function in conscious dogs instrumented for the measurement of LV and arterial pressures, LV diameter, and calculations of indexes of myocardial contractility. With infusions of NE, significant hemodynamic changes were observed only when plasma levels of NE exceeded 1,000 pg/ml. While statistically significant, the increase in rate of rise of LV pressure (LV dP/dt) at these levels was relatively slight, i.e., 8 +/- 2.3%. With further increases in catecholamines (greater than 1,000 pg/ml) good correlations were observed with increases in arterial pressure and myocardial contractility. Similar results occurred with infusions of Epi. Moderate treadmill exercise doubled LV dP/dt, while NE and Epi rose by only 563 +/- 128 and 292 +/- 50 pg/ml, respectively. Hemorrhage (30 ml/kg) decreased all indexes of contractility but increased plasma NE by 1,108 +/- 206 pg/ml and Epi by 1,475 +/- 266 pg/ml. Despite arterial NE and Epi levels 10-20 times those during exercise, infusions were unable to reproduce the peak changes in contractility seen with exercise. Infusions of NE or Epi to equal the plasma levels during exercise increased contractility by only 5-10%. In view of the marked disparity between levels of circulating catecholamines and LV function during exercise, hemorrhage, and catecholamine infusion, we conclude that circulating catecholamines do not adequately reflect the degree of inotropic stimulation to the myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of oxygen radicals on cerebral arterioles
Authors: Wei E. P. , Christman C. W. , Kontos H. A. , Povlishock J. T.
Published: December 2017

Xanthine oxidase and xanthine, a combination that produces hydrogen peroxide and superoxide anion radical, applied topically in anesthetized cats equipped with cranial windows caused arteriolar dilation during application, sustained dilation 1 h after washout, and reduced reactivity to the vasoconstrictive effects of arterial hypocapnia, discrete lesions of the endothelium, and morphological abnormalities of the vascular smooth muscle by electron microscopy. Similar effects were seen in small, but not in large, arterioles during topical application of hydrogen peroxide or hydrogen peroxide plus ferrous sulfate, a combination that produces free hydroxyl radical. The functional changes caused by xanthine oxidase plus xanthine were inhibited completely by superoxide dismutase plus catalase. Superoxide dismutase or catalase, each by itself, eliminated the residual effects seen after washout and reduced the dilation during application of xanthine oxidase. The results show that superoxide anion radical and hydrogen peroxide produce reversible arteriolar dilation and that consistent vascular damage is produced in the presence of both superoxide anion radical and hydrogen peroxide.
Function of the pericardium and pericardioperitoneal canal in elasmobranch fishes
Authors: Shabetai R. , Abel D. C. , Graham J. B. , Bhargava V. , Keyes R. S. , Witztum K.
Published: December 2017

Previous studies of cardiac function in elasmobranch fishes have not included the influence of the pericardioperitoneal canal on pericardial pressure and volume and thus on cardiac function. Accordingly, we studied the function of the pericardium and pericardioperitoneal canal in sharks and rays. We found negative pericardial pressure that rose to a plateau of approximately 0 mmHg when fluid was infused into the pericardium with the canal undisturbed. However, this pericardial pressure elevation caused severe cardiac tamponade. After the canal was occluded, the pressure plateau was substituted with an exponential rise. We injected radioisotopes into the pericardial cavity and obtained scintigrams several hours later. The scans and counts of body fluids and tissues indicated absorption, disputing the suggestion that the primary function of the canal may be inadequate absorption of pericardial fluid. We conclude that the pericardioperitoneal canal maintains negative pericardial pressure, which is a prerequisite in elasmobranch fishes and may serve to regulate pericardial pressure level to optimize cardiac function in relation to changes in cardiac size.