Alpha adrenergic constriction of coronary arteries in conscious dogs.
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Biomedical subjects
Publications and source records attributed to M Pagani.
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The effects of intravenous infusion of nitroglycerin (NTG), 8 and 32 microgram/kg.min for 7 min, and of sublingual NTG, 1.2 mg, were examined on direct and continuous measurements of systemic, coronary, and regional hemodynamics, left ventricular (LV) dimensions, pressures, and myocardial contractility in conscious dogs. NTG induced sustained reductions in LV dimensions and transient increases in heart rate and dP/dt, and decreases in mean arterial pressure. Initially NTG increased cardiac output and flows to the coronary, mesenteric, renal, and iliac beds, while systemic and regional vascular resistances fell. Later, cardiac output, cardiac work, and mesenteric and iliac flows fell significantly below control, and significant vasoconstriction in the systemic as well as mesenteric, iliac, and coronary beds was observed at a time when LV end-diastolic dimensions were still significantly reduced. Peripheral vasoconstriction was not observed with systemic NTG in deafferented dogs or when NTG, 1 microgram/kg.min, was infused intra-arterially into the iliac bed. Thus, systemic NTG induces a biphasic response consisting of initial arteriolar vasodilation followed by vasoconstriction in the mesenteric, iliac, coronary and systemic beds, which is presumably due to longer lasting effects on preload and to secondary reflex responses to the drug.
This paper describes the development of several important modifications that were incorporated into the ultrasonic, transit-time dimension system in order to obtain multiple simultaneous, instantaneous, and continuous measurements of the external dimensions of the aorta and its major branches in conscious, unrestrained animals. At operation a pair of small piezoelectric crystals was sutured to arterial adventitia, and a miniature pressure gauge was implanted in the vessel at the same cross-sectional plane. After recovery from surgery, wall motion was not altered appreciably and scarring was minimal. This technique allows long-term monitoring of aortic pressure-dimension relations and is applicable for small (fetal and neonatal) as well as large (adult dogs and sheep) animals. When vessel wall thickness is measured, stress-radius analysis can be performed so as to compute vascular elastic stiffness as a function of stress. Moreover, the suitability for radiotelemetry of the pressure and dimension signals measured with this technique enables the study of these parameters in unrestrained animals, e.g., during spontaneous severe exercise.
The hemodynamic effects of 7 min i.v. sodium nitroprusside (NP) were studied in conscious dogs previously instrumented for measurement of arterial pressure, cardiac output, regional blood flow distribution, left ventricular (LV) pressure, and internal dimensions. Nitroprusside, 25 microgram/kg/min, reduced mean arterial pressure by 23 +/- 3%. Cardiac output increased initially by 39 +/- 7% and returned toward control by the end of the infusion. Regional blood flows increased initially; the relative rise was greatest in the coronary (+ 225 +/- 39%), intermediate in the mesenteric (+ 98 +/- 23%) and iliac (+ 38 +/- 6%), and least in the renal (+ 10 +/- 3%) bed. By the end of the infusion period the vasodilation was unchanged in the iliac bed, less intense in the coronary and mesenteric, while in the iliac bed, blood flow was reduced and resistance was actually increased by 33 +/- 11% above control. A generalized vasonconstriction ensued after cessation of infusion. In contrast, when the drug was administered intra-arterially to the iliac bed, arterial pressure did not fall and only iliac vasodilation was observed. Peak cardiac effects were characterized by increases in heart rate and LV dP/dt, along with marked reduction in LV end-systolic diameter (- 13 +/- 2%), and in end-diastolic diameter (-17 +/- 2%) and pressure. LV end-diastolic diameter fell even heart rate was maintained at a constant rate by pacing. Thus, in the conscious dog, NP reduced LV dimensions substantially, while inducing changes in peripheral beds. The differences in these effects depend on interactions between the direct effects of NP and the opposing effects of reflex adjustments which appear sufficiently powerful to result in net constriction of the iliac bed late during the infusion.
The changes in left ventricular (LV) dynamics induced by brief periods of ischemia (100 seconds) and subsequent reperfusion were analyzed in conscious dogs. Global LV ischemia, induced by partially occluding the left main coronary artery, reduced LV flow homogeneously and impaired LV function as reflected by decreases in LV stroke "work" (89 +/- 4% M +/- SE), systolic shortening (72 +/- 4%), velocity of shortening (56 +/- 6%), LV systolic pressure (34 +/- 5%), and dP/dt (59 +/- 6%). Regional LV ischemia, induced by occluding either the left circumflex or anterior descending coronary artery completely, reduced flow to the ischemic segment (82 +/- 3%) while decreasing segment work (96 +/- 5%), shortening (82 +/- 3%), and velocity of shortening (70 +/- 5%), with minimal depression of overall LV function. In both groups the extent of shortening was reduced more rapidly and greater (P less than 0.01) than shortening velocity. Moreover, with localized ischemia, segment work was reduced more (P less than 0.01) than shortening. With reperfusion, a transient overshoot in function above preischemic control levels was observed in both groups (global work increased by 60 +/- 12% and regional work by 28 +/- 4% above control). This overshoot was not dependent on adrenergic mechanisms, but was prevented by inhibiting reactive hyperemia. Thus myocardial ischemia induces a dissociation between extent and rate of myocardial shortening. A further dissociation between shortening and work is apparent with regional ischemia. After reperfusion there is a transient overshoot in function which appears to be dependent upon the associated reactive hyperemia.
The effects of coronary occlusion and of subsequent propranolol administration were examined in 18 conscious dogs. Overall left ventricular (LV) function was assessed by measurements of LV pressure and dP/dt, and regional myocardial function was assessed by measurements of segment length (SL), velocity of SL shortening and regional myocardial "work", i.e., pressure-length loops in normal, moderately, and severely ischemic zones. Regional intra-myocardial electrograms were measured from the same sites along with regional myocardial blood flow as determined by the radioactive microsphere technique. Coronary occlusion resulted in graded loss of function from the normal to severely ischemic zones with graded flow reduction and graded elevation of the ST segment. Propranolol depressed overall LV function, function in the normal zone (work fell by 17+/-4%), and in the majority of moderately ischemic segments (work fell by 7+/-3%). In severely ischemic segments the extent of paradoxical motion and post-systolic shortening was reduced by propranolol. After propranolol regional myocardial blood flow fell in the normal zone (11+/-2%) and rose in the moderately (15+/-4%) and severely (63+/-10%) ischemic zones. Thus, in the conscious dog with regional myocardial ischemia, propranolol induces a redistribution of myocardial blood flow, with flow falling in normal zones and rising in moderately and severely ischemic zones. The improvement in perfusion of ischemic tissue was associated with slight but significant depression of shortening, velocity, and work in the moderately ischemic zones and of paradoxical bulging and post-systolic shortening in the severely ischemic zone.
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1. We recorded the electrical impulse activity of thirty-five single afferent fibres with aortic endings isolated from the third to the sixth left thoracic sympathetic rami communicantes of anaesthetized cats. The endings of each fibre were localized by mechanical probing of the opened aorta at the end of each experiment. 2. Twenty-four fibres had a single aortic receptive field. Eleven fibres had several and distinct receptive fields (from two to four): they were usually located in nearby aortic areas or, in addition, in other proximal portions of the arterial tree or in the adjacent pleura and connective tissue. 3. Twenty-nine fibres had conduction velocities ranging between 5 and 27 m/sec (Group Adelta), while six fibres had conduction velocities between 0-2 and 1-2m/sec (Group C). 4. The spontaneous impulse activity was in phase with the aortic pressure pulse and consisted of not more than one impulse per pressure pulse. It was increased during increases in aortic pressure and, conversely, decreased during decreases in aortic pressure. In vivo and post mortem studies showed that these mechanoreceptors had an impulse activity which rapidly adapted during sustained stimuli. They thus seem to signal pulsatile aortic stretch. 5. These aortic sympathetic afferents are likely to be part of a nervous pathway through which pressor reflexes, exhibiting positive feed-back characteristics, can elicited.
The reflex tachycardia elicited by rapid intravenous infusions of a blood substitute was studied in 21 chronic cats with spinal sections at C8. All animals could breath spontaneously. The day after section the average resting heart rate (HR) and arterial pressure (AP) were 109 beats/min and 98/67 mmHg, respectively. Vagal blockade with atropine (0.5-0.7 mg/kg iv) was performed prior to each infusion, increasing the average HR To 127 beats/min. In 39 infusions in 21 cats the average increase in HR was 10 beats/min (range from -6 to +22 beats/min). A tachycardia was observed in all but five trials, four of which were obtained in two cats that subsequently responded with a tachycardia. In seven animals the neural circuit mediating the response was partially or totally interrupted by section of several thoracic dorsal roots (T1-T4 or T1-T6) and of the spinal cord at the inferior level of these sections (between T6 and T7). The tachycardia response was progressively reduced and finally abolished by these procedures. These experiments indicate that spinal neural mechanisms are likely to contribute to the phenomenon first described by Bainbridge.
The synthesis of carrier ampholytes suitable for isoelectric focusing is described. The mixture of hexamethylenetetramine (HMTA), triethylenetetramine (TETA), tetraethylenepentamine (TEPA) and pentaethylenehexamine (PEHA) ampholytes closely resembles commercial Ampholine, and covers the pH range 3-9.5. We have been able to detect focused ampholytes in a gel slab, taking advantage of their different refractive indices, and to assess their relative amounts along the pH gradient. PEHA ampholytes contain up to 20% of chromophoric structures, with two UV peaks at 368 and 315 nm, in a pH-dependent equilibrium, associated with a very weak nitrogen function having a pK of 1.1. This could be the pK6 of the last amino group in PEHA. However, NMR spectra failed to reveal any nitrogen heterocyclic structure formed during the synthesis. This mixture of ampholytes exhibits good conductivity, produces smooth pH gradients and allows sharp protein separations in the pH range 3-9.5. Their synthesis is very easy and their cost is extremely low. Their availability sould make feasible large-scale preparative isoelectric focusing, and attract more interest to continuous-flow techniques, where large amounts of ampholytes are required.
A simple method for fractionating synthetic carrier ampholytes is reported, based on the principle of continuous-flow isoelectric focusing in gel-stabilized layers. An 8% ampholyte solution, encompassing the pH range 3-9.5, is separated into 12 fractions in a chamber filled with Sephadex G-100 by a continuous-flow technique. We are thus able to obtain ampholytes of narrow pH range, encompassing approximately 2 pH units, whose resolving power is comparable with that obtained with commercial Ampholine covering similar pH ranges.
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1. In vagotomized anaesthetized cats with both common carotid arteries occluded, stretch of the thoracic aorta induced reflex increases in arterial blood pressure, heart rate and left ventricular dP/dtmax. Similar responses were obtained in cats with spinal transection at the level of the first cervical nerve roots. 2. The hypothesis is advanced that sympathetic excitatory reflexes may contribute to the maintenance of hypertension through positive feedback.
In anesthetized vagotomized cats with the chest opened and artificially ventilated, aortic blood pressure (AP) and external diameter (AD; ultrasound technique) were measured in the proximal third of the descending thoracic aorta. Slow sinusoidal oscillations (0.2-0.3 Hz in aortic volume were produced by a piston pump connected to a femoral artery. Diastolic pressure-diameter relationship (PDR) curves were obtained during control conditions and during stimulation of either the cut central end of the left inferior cardiac nerve (ICN) or the decentralized thoracic sympathetic chain (SC). In six cats with both carotid arteries occluded ICN stimulation reflexly shifted the PDR curves to lower diameters for any given pressure (mean deltaAD 3.2% at control AP). A smaller response to ICN stimulation was obtained in five cats with one patent carotid artery (mean deltaAD 2.3% at control AP). Stimulation of sympathetic efferents to the aorta (SC) caused similar responses in five animals (mean deltaAD 3.4% at control AP). This reflex control of the thoracic aorta may be involved in cardioaortic coupling and may influence the sensitivity of aortic mechanoreceptors.
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