Effects of sympathetic nerve stimulation on cerebral blood flow.
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Animals↗
Biomedical subjects
F M Abboud
Publications and source records attributed to F M Abboud.
Regulation of total and regional spinal cord blood flow.
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Animals↗
Effects of angiographic contrast media on sino-atrial nodal function.
Injection of meglumine diatrizoate (Renografin-76) into the selectively perfused sinus node artery of the dog produces bradycardia which is unaltered by autonomic blockade or by changes in sinus node artery pressure. Contrast agents and other hyperosmolar substances prolong the R-R interval in proportion to their osmolarity. Selective injection of contrast media into other cannulated segments of the coronary tree produces no change in heart rate. Transfemoral arteriography, however, produces bradycardia with both right and left coronary injections. Both direct and reflex sinus node depression occur with coronary arteriography in the dog. Direct effects are mediated by hyperosmolarity.
Adrenergic beta-Antagonists↗
Effects of time on volume and distribution of coronary collateral flow.
Changes in the volume and distribution of collateral blood flow were studied during the 1st h after coronary occlusion in nine open-chest dogs. Labeled microspheres (7-10 mum) were injected into the left atrium prior to and 20 s, 5 min, and 60 min after acute occlusion of the midcircumflex coronary artery so that myocardial perfusion to small segments of the entire left ventricle could be measured. The segmental perfusions were classified as normally perfused, severely hypoperfused, moderately hypoperfused, and borderline hypoperfused. Standard hemodynamic measurements were obtained and relative coronary vascular resistance to the normally perfused and hypoperfused zones was calculated. The principal conclusions of the study are as follows: 1) during the 1st h after coronary occlusion the collateral flow to the hypoperfused myocardium increases substantially; 2) the increase in collateral flow is distributed fairly evenly to various hypoperfused zones and is associated with a marked decrease in coronary vascular resistance; and 3) as a result of this influx in collateral flow the size of the hypoperfused area decreases and the relative proportion of severely hypoperfused segments within the hypoperfused area decreases.
Animals↗
Total and regional cerebral blood flow measurement with 7-10-, 15-, 25-, and 50-mum microspheres.
Cerebral arteriovenous shunting of 7-10-, 15-, 25-, and 50-mum labeled microspheres was studied in 12 anesthetized dogs. Approximately 8% of the 7-10-mum spheres were shunted to cerebral venous blood, whereas less than 2% of the 15-, 25-, and 50-mum spheres were shunted. Cerebral vascular dilatation induced by hypoxia or hypercapnia did not alter the shunting. The calculated total cerebral flow was 10-15% lower with 7-10-mum microspheres as compared with simultaneous flows measured with the larger microspheres which also suggests that 7-10-mu spheres were shunted through the brain. The calculated distribution of cerebral flow was similar with 7-10- and 15-mum spheres but markedly altered when 50-mum spheres were used. Repeated injections of 15-mum spheres were used. Repeated injections of 15-mum microspheres given under stable conditions yielded total cerebral blood flows which averaged +/- 6% of their respective mean and the regional distribution of flow was highly reproducible. These data suggest that, in dogs, 15-mum spheres are an appropriate size to use to measure cerebral blood flows, since shunting is minimal, the distribution is not artifactually distorted, and the measurements are reproducible.
Animals↗
Modulation of carotid baroreflex responsiveness in man: effects of posture and propranolol.
Carotid baroreceptors were stimulated with graded neck suction in supine and standing volunteers, before and after autonomic blockade, to determine the influence of posture on baroreflex responsiveness. Propranolol significantly augmented baroreflex pulse interval prolongation in the supine position. Upright posture did not modify baroreflex pulse interval responses prior to propranolol, but significantly augmented responses after propranolol. The results suggest that standing enhances baroreflex sensitivity, but that under normal circumstances, this effect is masked by beta-adrenergic stimulation. Augmentation of baroreflex pulse interval prolongation in the supine and standing positions by propranolol may contribute to the effectiveness of this drug in angina pectoris and labile hypertension.
Adult↗
Effect of intra-aortic balloon counterpulsation on the motion and perfusion of acutely ischemic myocardium. An experimental echocardiographic study.
The effect of intra-aortic balloon counterpulsation (IABC) on the motion and perfusion of ischemic left ventricular posterior myocardium was studied in 30 open-chest dogs, using ultrasound to register motion and 7-10 mu radioactive microspheres to determine perfusion. Circumflex coronary artery ligation produced acute aneurysmal bulging during isovolumetric contraction and diminished ischemic wall velocity during systolic ejection. Myocardial perfusion was determined in five dogs; perfusion of the area supplied by the ligated coronary artery fell from a control value of 72.9 +/- 13.8 (SE) to 30.0 +/- 2.3 cc/100 g/min (P less than 0.05) at 5 minutes after coronary occlusion. IABC was then administered for one hour, with a fall in aortic systolic pressure (112 +/- 6 to 105 +/- 7 mm Hg, P less than 0.05) and rise in peak aortic diastolic pressure (94 +/- 6 to 102 +/- 7 mm Hg, P less than 0.05). Despite this the ischemic area showed no change in perfusion (measured at the same time): 30.0 +/- 2.3 to 28.0 +/- 2.4 cc/100 g/min. Little change in wall motion occurred: aneurysmal bulging decreased modestly (4.5 +/- 0.3 to 3.6 +/- 0.3 mm, P less than 0.05), but ischemic wall velocity did not increase. After cessation of counterpulsation and one hour of coronary reperfusion aneurysmal bulging disappeared and wall velocity improved. The addition of norepinephrine (eight dogs) or nitroprusside (seven dogs) to intraaortic balloon counterpulsation did not cause a significant further improvement in the response of the dyskinesis during the period of ischemia. We conclude that IABC has little effect on ischemic dyskinesis, probably due to its failure to improve perfusion of the acutely ischemic myocardium.
Acute Disease↗
Limitations of thallium-201 myocardial perfusion scintigrams.
The reliability of myocardial perfusion scintigrams with thallium-201 (201Tl) for detecting areas of hypoperfusion was assessed in 16 closed-chest dogs. Variable areas of ischemia were produced either by occluding or stenosing the left anterior descending coronary artery. Cardiac scintigrams taken in four projections were compared with regional myocardial perfusion maps. Segmental concentrations and segmental perfusions were quantitated by counting the emissions from 201Tl and the microspheres in each of 96 segments of the left ventricle. In addition, studies with a phantom were performed. The results indicate: 1) The emissions from 201Tl and from microspheres correlated well in ischemic segments (r = 0.93 +/- SE 0.02). 2) Seven of twelve ischemic hearts had definitely abnormal scintigrams and in each of these the hypoperfused zone was greater than 4.9 grams and perfusion was decreased by more than 45%. 3) In the phantom, abnormal scintigrams could be detected in the presence of lesser deficits than in the dogs. The limitation of the thallium perfusion scintigrams will be the inconsistent detection of small perfusion deficits.
Animals↗
Relationships between myocardial perfusion, myocardial necrosis, and technetium--99m pyrophosphate uptake in dogs subjected to sudden coronary occlusion.
The quantitative relationship between abnormalities seen on technetium-99m pyrophosphate (99mTc-PYP) infarct scintigrams and the size of the myocardial infarction is unclear. We evaluated two possible determinants of 99mTc-PYP accumulation: myocardial perfusion measured with 7-10 mu microspheres and the extent of necrosis determined histologically. Hemodynamics and myocardial perfusion to small segments of the left ventricle were measured prior to, 5-10 min, and 44-48 hours following sudden occlusion of the left anterior descending coronary artery in ten awake dogs. 99mTc-PYP was injected i.v. following the third injection of microspheres and the animals were killed 2 hours later. The important findings were as follows: 1) there is a close relationship between the extent of myocardial necrosis observed and the perfusion of segments 5-10 min following coronary occlusion; and 2) that segmental myocardial perfusion is an important determinant of 99mTc-PYP accumulation by myocardial segments which contain areas of necrosis. Although the present data preclude statistical analysis of the relationship between the level of necrosis in a segment and the accumulation of 99mTc-PYP by that segment, the two do not appear to be related, a finding which would discourage use of intensity of 99mTc-PYP images for infarct size. The distribution of an abnormality on the scintigram may provide an estimate of infarct size. However, the geometry of the infarct and the resolving power of the scanning equipment will significantly limit this in many clinical situations.
Animals↗
Effects of acute coronary occlusion on the motion and perfusion of the normal and ischemic interventricular septum.
To establish the effect of local and remote myocardial ischemia on interventricular septal motion, 27 open-chest dogs were studied using ultrasound and radioactive microspheres. In 14 dogs the left anterior descending coronary artery was ligated. If the ultrasound beam traversed ischemic septum (proximal LAD occlusion), significant (P less than 0.05) declines in systolic septal velocity (26.4 +/- 2.9 to 6.4 +/- 1.8 mm/sec), and excursion (2.6 +/- 0.3 to 0.7 +/- 0.2 mm) occurred, and systolic thickening was reduced. Similar significant changes were seen when the ultrasound beam traversed nonischemic septum adjacent to the ischemic area (distal LAD occlusion). In 13 additional dogs, circumflex coronary ligation produced posterior ischemia. The mean septal velocity for this group increased significantly (21.8 +/- 2.6 to 26.5 +/- 3.3 mm/sec), as did the septal excursion (2.5 +/- 0.2 to 3.1 +/- 0.4 mm). We conclude that acute LAD occlusion causes a reduction in systolic velocity, excursion, and thickening of both the involved ischemic and the adjacent nonischemic septum. When myocardial ischemia was produced in a part of the ventricle remote from the septum, septal velocity and excursion increased.
Animals↗
Effect of stimulation of carotid chemoreceptors on total and regional cerebral blood flow.
This study was performed to determine whether stimulation of the carotid chemoreceptors increases total or regional cerebral blood flow and whether activation of arterial chemoreceptors contributes to cerebral vasodilation during systemic hypoxemia. In anesthetized and ventilated dogs, carotid chemoreceptors were stimulated with nicotine or hypoxic and hypercapnic blood. To measure total and regional cerebral blood flow, we used labeled 15-mu microspheres. Stimulation of chemoreceptors did not increase cerebral blood flow or produce significant redistribution of cerebral blood flow, even though the chemoreflex was intact in these animals (as manifested by vasoconstriction in muscle, kidney, and small bowel) and the cerebral vessels dilated in response to systemic hypercapnia. In other studies in anesthetized, ventilated dogs and rhesus monkeys, cerebral vasodilator responses to systemic hypoxemia were observed before and after denervation of carotid and aortic chemoreceptors. Systemic hypoxemia produced large and equivalent increases in cerebral blood flow before and after chemodenervation. We conclude that stimulation of carotid chemoreceptors does not produce cerebral vasodilation and that chemoreceptors do not contribute significantly to cerebral vasodilation during systemic hypoxemia.
Animals↗
Phentolamine and isoproterenol: comparison of effects on vascular resistance and oxygen uptake in skeletal muscle during hypotension.
Effects of drugs on precapillary vessels and oxygen uptake may differ from effects on resistance vessels and total flow in skeletal muscle. This study was performed to compare effects of phentolamine and isoproterenol, two drugs which are used to treat shock, on oxygen uptake in skeletal muscle. Oxygen uptake of gracilis muscle (GVO2) was measured in muscles perfused at constant flow or constant pressure in normotensive dogs. We compared effects of the drugs on oxygen uptake at doses chosen so that both drugs produced comparable effects on vascular resistance. With flow constant, phentolamine increased but isoproterenol decreased or did not alter GVO2. With constant pressure, phentolamine produced significantly greater increases in GVO2. For example, increases in GVO2 occurred with all three doses of phentolamine, but only with the high dose of isoproterenol. Neither drug altered oxygen-hemoglobin affinity of red blood cells or oxygen consumption of skeletal muscle in vitro. The results suggest that phentolamine produces more favorable effects than isoproterenol on oxygen uptake in skeletal muscle, presumably because of greater dilator action on precapillary sphincters.
Animals↗
Effect of baroreceptor activity on ventilatory response to chemoreceptor stimulation.
This study tested the hypothesis that ventilatory responses to chemoreceptor stimulation are affected by the level of arterial pressure and degree of baroreceptor activation. Carotid chemoreceptors were stimulated by injection of nicotine into the common carotid artery of anesthetized dogs. Arterial pressure was reduced by bleeding the animals and raised by transient occlusion of the abdominal aorta. The results indicate that ventilatory responses to chemoreceptor stimulation were augmented by hypotension and depressed by hypertension. In additional studies we excluded the possibility that the findings were produced by a direct effect of changes in arterial pressure on chemoreceptors. Both carotid bifurcations were perfused at constant flow. In one carotid bifurcation, perfusion pressure was raised to stimulate carotid sinus baroreceptors. In the other carotid bifurcation, pressure was constant and nicotine was injected to stimulate carotid chemoreceptors. Stimulation of baroreceptors on one side attenuated the ventilatory response to stimulation of contralateral chemoreceptors. This inhibition was observed before and after bilateral cervical vagotomy. We conclude that there is a major central interaction between baroreceptor and chemoreceptor reflexes so that changes in baroreceptor activity modulate ventilatory responses to chemoreceptor stimulation.
Animals↗
Three dimensional geometry of acutely ischemic myocardium.
The distribution of coronary flow to small segments of the entire left ventricle (96 per dog; average weight = 0.78 g) was studied in 28 open-chested dogs utilizing 7-10 mu labeled microspheres. Although the flow to large areas of the ventricle was nearly evenly distributed, there was considerable heterogeneity of flow to small adjacent segments of myocardium (average standard deviation of the flow distributions was 17.3 +/- 3.2% of mean lfow). Approximately one-half of the measured heterogeneity of flow could be attributed to various extraneous factors, and one-half appears to be due to inherent heterogeneity of flow in the left ventricular myocardium. In ten of 28 dogs, the mid-circumglex coronary was suddenly occluded, and five minutes thereafter the distribution of left ventricular flow was determined with microspheres labeled with a different isotope. The ischemic regments were separated into three groups: severely ischemic, moderately ischemic, and borderline ischemic. The three dimmensional geometry of the acutely ischemic myocardium was analyzed, and four general conclusions were reached. 1) The percent distribution of severely ischemic segments, moderately ischemic segments, and borderline ischemic segments within an ischemic region varies from animal to animal. 2) Subendocardial segments were more frequently and more severely affected than neighboring mid-wall or epicardial segments. 3) No evidence of an "hyperperfused zone" of myocardium surrounding the ischemic area was found. 4) The flows to segments immediately adjacent to the severely ischemic segments were heterogeneous. Therefore, the concept of a geometrically defined "buffer zone" of moderately ischemic myocardium surrounding and separating severely ischemic from normally perfused myocardium no longer seems realistic.
Animals↗
Correlation between echocardiographically demonstrated segmental dyskinesis and regional myocardial perfusion.
In order to evaluate the relationship between regional myocardial perfusion and segmental dyskinesis, 22 open chest dogs were studied using ultrasound to register cardiac wall motion and radioactive labeled microspheres to determine myocardial perfusion. In six dogs, motion and perfusion were correlated at two levels of partial circumflex coronary artery occlusion followed by complete occlusion. A good correlation between declining myocardial perfusion of all the ischemic segments and development of aneurysmal bulging (during isometric contraction) was seen: r = minus 0.80. A similar correlation between myocardial perfusion and endocardial wall velocity (during systolic ejection) was observed: r = 0.92. In nine dogs, the effect of 45 minutes of complete coronary occlusion followed by 30 minutes of reperfusion was evaluated with respect to perfusion and motion. After coronary reperfusion myocardial perfusion of the ischemic area returned to control levels (from 32.6 +/- 3.5 to 130.3 +/- 13.3 ml/100 g/min), but aneurysmal bulging during isometric contraction persisted. Endocardial wall velocity during systolic ejection showed a variable response to reperfusion, achieving values ranging from 32% to 162% of the preocclusion levels. In seven dogs the ultrasound beam was reflected off nonischemic myocardium adjacent to areas of ischemia resulting from coronary occlusion. Despite preservation of normal myocardial perfusion in these nonischemic areas wall motion abnormalities were evident: endocardial wall velocity declined from 25.8 +/- 5.8 to 14.0 +/- 4.9 mm/sec (P less than 0.01), and aneurysmal bulging in three animals. These changes may be due to transient undetected ischemia in the segments struck by the ultrasound beam, or to passive alteration of the motion of the normally perfused areas by the severe dyskinesis of the adjacent ischemic myocardium.
Animals↗
Effect of alterations of arterial blood pressure and heart rate on segmental dyskinesis during acute myocardial ischemia and following coronary reperfusion.
The effect of alterations of blood pressure and heart rate on segmental dyskinesis induced by coronary artery ligation and the influence of such manipulations on the magnitude of recovery of the syskinetic segment during subsequent coronary artery reperfusion were evaluated in 77 open-chest dogs. Wall motion was recorded by ultrasound reflected directly from the ischemic myocardial segment. Acute ischemia produced characteristic regional abnormalities in wall motion: aneurysmal bulging occurred during isometric contraction and wall velocity was markedly reduced during ventricular ejection. During 69 minutes of ischemia, a control group of dogs underwent no interventions and showed no further changes in wall motion. Tachycardia induced by atrial pacing during ischemia had no significant effect. Arterial hypertension during ischemia caused a marked reduction in wall velocity when methoxamine was used: 14 plus or minus 2 (SE) mm/sec (ischemia alone) to 6 plus or minus 1 mm/sec (ischemia + drug). In contrast, norepinephrine improved wall velocity: 11 plus or minus 2 mm/sec (ischemia alone) to 25 plus or minus 4 mm/sec (ischemia + drug). Hypertension caused by infusion of phenylephrine gave intermediate results, as did hypotension induced by either nitroprusside or hemorrhage during the ischemic period. After 60 minutes the drugs were stopped, the coronary ligation released, and the ischemic myocardium reperfused. The relative order of improvement of wall velocity with reperfusion was 11 plus or minus 2 mm/sec (ischemia alone) to 24 plus or minus 3 mm/sec (reperfusion) in the group that received norepinephrine, 12 plus or minus 3 mm/sec to 20 plus or minus 3 mm/sec in the control group with no intervention durin ischemia, 13 plus or minus 2 mm/sec to 20 plus or minus 1 mm/sec in the nitroprusside group, 9 plus or minus 2 mm/sec in the phenylephrine group, and 14 plus or minus 2 mm/sec to 12 plus or minus 1 mm/sec in the methoxamine group. The aneurysmal bulging during isometric contraction also was reduced to a greater degree by reperfusion in the group that received norepinephrine during the ischemic period than it was in the groups undergoing other interventions during ischemia. We conclude that drug-induced elevations in arterial blood pressure can have different effects on the syskinetic motion of acutely ischemic myocardium and on the degree of recovery following reperfusion depending on the particular agent used.
Animals↗
In vitro acetylcholine biosynthesis in normal and failing guinea pig hearts.
Choline acetyltransferase activity, which is rate limiting in acetylcholine biosynthesis, was measured in the four heart chambers of guinea pigs subjected to (1) sham surgery, (2) constriction of the ascending aorta, (3) constriction of the descending thoracic aorta, and (4) constriction of the pulmonary artery. After 30 days when hypertrophy and heart failure were fully established, choline acetyltransferase was quantified in vitro by a radiochemical assay. In the sham-operated group, enzyme activity expressed in terms of unit weight of cardiac tissue was greatest in the right atrium and the right ventricle and lower in th left atrium and the left ventricle (3.62 plus or minus 0.30, 2.96 plus or minus 0.52, 1.64 plus or minus 0.15, and 1.67 plus or minus 0.22 nmoles/min g-1, respectively). Enzyme activity was reduced (P less than 0.05) in the right atria and the right ventricles of guinea pigs with constriction of the pulmonary artery (1.68 plus or minus 0.37 and 1.31 plus or minus 0.29 nmoles/min g-1, respectively). Enzyme activity also tended to be reduced in the left atria and the left ventricles of guinea pigs with constriction of the aorta. These changes represented a relative dilution of enzyme activity per unit weight but not an absolute depletion, since choline acetyltransferase activity per ventricle was not reduced. The absence of significant changes in the total amount of the neuronal enzyme, choline acetyltransferase, per ventricle contrasted with the observed increases in the myocardial enzyme, carnitine acetyltransferase. These results confirm the presence of significant parasympathetic innervation of the ventricles as well as the atria but do not demonstrate alterations in parasympathetic neurotransmitter biosynthesis in hypertrphied and failing myocardium. The absence of absolute reductions in choline acetyltransferase activity in hypertrophied and failing ventricle contrasts strikingly with the previously reported reductions in tyrosine hydroxylase, which is rate limiting in sympathetic neurotransmitter biosynthesis.
Acetyl Coenzyme A↗
Effects of high and low sodium intake on arterial pressure and forearm vasular resistance in borderline hypertension. A preliminary report.
The purpose of this study was to evaluate effects of high and low sodium intake on arterial pressure and forearm vascular resistance in subjects with borderline hypertension and to compare responses to sodium excess in these subjects with responses in a recent study in normotensive subjects. Six subjects with borderline hypertension were studied after ten days of high (410 mEq/24hr) and low (10mEq/24hr) sodium intake. Potassium intake was constant. In five of six subjects, high sodium intake decreased forearm blood flow and increased forearm vascular resistance and arterial pressure. During low and high sodium intake forearm blood flow averaged 7.8 plus or minus 1.2 (SE) and 5.9 plus or minus 0.8 ml/min x 100 ml, respectively; forearm vascular resistance averaged 13.5 plus or minus 2.2 and 19.1 plus or minus 3.0 units, respectively; and mean arterial pressure averaged 89 plus or minus 3 and 98 plus or minus 2 mm Hg, respectively. High sodium intake augmented forearm vasoconstrictor responses to lower body negative pressure, a stimulus to neurogenic vasoconstriction. The results contrast with our earlier results in normotensive subjects in whom sodium excess produced forearm vasodilatation and failed to increase arterial pressure significantly. Decreases in renin and aldosterone with high sodium intake were similar in the two groups. The results suggest that excessive sodium intake in subjects with borderline hypertension produces abnormal increases in forearm vascular resistance, neurogenic vasoconstriction, and arterial pressure. The reasons for the contrast between the borderline hypertensives and normotensives are unknown, but they do not seem to be related to the renin-angiotensin-aldosterone system.
Adult↗