Harold D. Green

Aortic pulse wave velocity, elasticity, and composition in a nonhuman primate model of atherosclerosis.

Aortic pulse wave velocity was determined in Macaca fascicularis monkeys fed either atherogenic or control diets for 36 months. The foot-to-foot velocity and apparent phase velocities of the second through seventh Fourier harmonics at a given diastolic pressure in the atherosclerotic monkeys were 1.5 to 2.0 times the values for the control animals. More than 80% of the aortic intimal surface of the atherosclerotic monkeys was covered with fibrous or fatty plaque, which approximately doubled wall thickness and wall thickness to radius ratio. Angiochemical evaluations showed no difference in collagen or elastin concentration (as a fraction of lipid and mineral-free dried aorta), but the atherosclerotic aortas were 1.5 to 2.0 times that of control in collagen and elastin content (defined as the absolute quantity beneath a square centimeter of intimal surface). Total cholesterol and calcium concentrations in the atherosclerotic aortas were more than 10 times the values for the control aortas. The static circumferential distensibility of the excised atherosclerotic aortas was significantly less than control, but there was no difference in incremental (Youngs) modulus of elasticity. The in vitro pressure-strain elastic modulus of the atherosclerotic aortas was more than twice that of control, which was predicted from the enhanced wave velocity. The significantly increased stiffness of the atherosclerotic arteries appeared to be due mainly to the increased wall thickness caused by the atherosclerotic plaques rather than to material changes described by Youngs modulus. Extensive medial damage, however, also was present and could have had a major influence on stiffness. Atherosclerosis therefore can result in increased aortic stiffening, detectable by pulse wave velocity, even if there is no change in the overall Youngs modulus of elasticity.

Reduction in Pulse Wave Velocity and Improvement of Aortic Distensibility Accompanying Regression of Atherosclerosis in the Rhesus Monkey

Subclavian-to-femoral artery pulse wave velocity, as a measure of aortic stiffness, was determined in 31 rhesus monkeys (Macaca mulatto) which were divided into three groups on athero-genic progression or regression diets: nine monkeys (IIA) were fed a high cholesterol diet for 38 months, resulting in an average plasma cholesterol concentration of 638 mg/dl; and 10 (IIBi) and 12 (IIC1) monkeys were fed the same progression diet followed by 24-month regression diets which were manipulated to maintain plasma cholesterol concentrations as close as possible to 300 and 200 mg/dl, respectively. Average pulse wave velocity at a diastolic blood pressure of 70 mm Hg was significantly greater (9.4 ± 1.0 (mean ± SEM) m/sec) in the IIA group than in the IIBi (6.3 ± 0.3) or IIC, (6.6 ± 0.3) groups, although four of the IIA monkeys had pulse wave velocities that were not significantly higher than the regression monkeys. Total thoracic plus abdominal aortic cholesterol concentration was significantly reduced from 10.2 ± 1.4 mg/g wet weight in the IIA group to 5.7 ± 0.6 (IIBi) and 4.6 ± 0.6m g/S wet weight (IIC2). The total percentage of thoracic plus abdominal aortic intimal surface covered with fibrous plus fatty plaque averaged 56.9 ± 9.2% (IIA) vs. 33.5 ± 6.7 (IIBi) and 35.0 ± 7.4% (IIC1). Collagen content beneath a given intimal square surface significantly increased from 4.59 ± 0.31 mg/ cm2 (IIA) to 6.46 ± 0.33 (HB,) and 6.49 ± 0.48 mg/cm2 (IIC1), whereas elastin content decreased from 9.47 ± 1.56 (IIA) to 6.58 ± 0.73 (IIBi) and 6.01 ± 0.39 mg/cm2 (IIC,). There was no significant difference in any parameter between the two regression groups. These studies suggest a functional improvement of aortic elastic properties with regression of atherosclerosis. When comparing groups, the improve-ment appears to follow the reductions in total aortic cholesterol concentrations and in the extent of total atherosclerotic plaque rather than alterations in the collagen: elastin ratio which, in fact, increased when arterial stiffness decreased with regression. Circ Res 47: 425-432, 1980.

A Square Wave Electromagnetic Flowmeter for Application to Intact Blood Vessels

A new type electromagnetic flowmeter which utilizes an alternating square wave magnetic field applied to the unopened blood vessel is described. It attains stability of baseline and sensitivity not possible with older D.C. and A.C. meters and therefore puts measurement of blood flow through the unopened vessel on a practical basis.

Baroreceptor Reflexes and Autoregulation of Cerebral Blood Flow in the Dog

Cerebral venous outflow was measured in anesthetized dogs at the confluence of the sagittal and straight sinuses, with the lateral sinuses occluded. Denervation of the carotid bifurcation increased systemic arterial pressure (+25.8; SE±7.7 mm Hg) and decreased cerebral vascular conductance (−0.018; SE±0.005 ml/min · mm Hg); stimulation of the carotid sinus nerve decreased systemic arterial pressure and increased cerebral vascular conductance. Graded constrictions of the common carotid arteries induced transient responses of the cerebral blood flow that were characteristic of an autoregulatory process. Plots of the steady-state pressures and flows during the decreases of perfusion pressure were concave toward the pressure axis, were similar before and after denervation of the carotid bifurcation, and were indicative of autoregulation. We conclude that pressoreceptors in the carotid bifurcation or other pressoreceptors in systemic vessels upstream from the carotid bifurcation are not necessary for the control of the “tone” of the cerebral vasculature or in the mechanism of the autoregulation of cerebral blood flow.

Effects of Autonomic Nerves and Their Mediators on the Coronary Circulation and Myocardial Contraction

Mean and phasic coronary flows were recorded simultaneously by an electromagnetic meter, and peripheral coronary pressure was recorded distally from the temporarily occluded descending branch of the left coronary artery. From the results of these studies we conclude that: 1. The sympathetic cardiac nerves, as does levarterenol, increase myocardial contraction, (indicated by a shorter, more abrupt systole and more rapid isometric relaxation), and cause a slight degree of coronary arteriolar dilation. 2. Parasympathetic fibers exert no significant effect, although acetylcholine diminishes coronary arteriolar tone and may slightly diminish ventricular contraction. 3. That measurements of mean coronary flow and resistance are relatively satisfactory for indicating changes in coronary arteriolar tone, but are of relatively little value in evaluating myocardial contraction.

Hemodynamics of Large and Small Vessels in Peripheral Vascular Disease

To evaluate the hemodynamics of large and small vessels in patients with complete arterial occlusion and patients with vasospasm, digital flow, digital pulse contour, small-vessel resistance, flow-to-pulse ratio, large-vessel pressure drop, pulse velocity, and distensibility were compared to values found in normal subjects.[see figure in the PDF file]In the normal subject following orally administered alcohol, small-vessel resistance decreased but large-artery pressure drop, pulse velocity, and distensibility of the capacity vessels were not altered significantly.In arterial occlusive disease, small-vessel resistance was essentially normal in the absence of small-vessel occlusion; a high large-artery pressure drop, rounded pulse contour, and decreased pulse amplitude were observed. These are interpreted as being due to the damping effect of the narrowed, elongated collateral flow pathway that develops around the site of the occlusion. Pulse velocity also was decreased whereas flow-to-pulse ratio was increased in patients with occlusive disease. Large-vessel hemodynamics were unchanged after alcohol, suggesting lack of effect of the dilator on the collateral vessels.In vasospasm there was evidence of increased large-artery and small-vessel resistance and decreased distensibility of the capacity vessels, all of which returned toward but not completely to normal following alcohol.Digital pulse amplitude was found not to correlate well with flow, particularly in patients with arterial occlusive disease.

Adrenergic Drugs and Blockade on Coronary Arterioles and Myocardial Contraction

The 3 adrenergic substances, epinephrine, levarterenol and isopropylarterenol, were injected into a coronary artery of anesthetized dogs while recording the coronary artery flow (electromagnetic meter) and pressure. The effects of these substances on the peripheral coronary pressure (PCP) were recorded by occluding the flow proximal to the pressure gage. All 3 substances caused a qualitatively similar increase in myocardial contraction and dilation of the coronary arterioles.

Nature of the Vasodilator and Vasoconstrictor Receptors in Skeletal Muscle of the Dog

Femoral blood flow and arterial pressure responses to stimulation of the lumbar sympathetic chain at L3, L4 and L5 were compared with responses to intra-arterial injections of l-epinephrine and l-norepinephrine before and after progressively increasing levels of adrenergic blockade, and after atropine. The vasoconstrictor responses to nerve stimulation resembled most closely those caused by l-norepinephrine injections at all levels of blockade. Atropine blocked the dilator responses to sympathetic nerve stimulation and reduced reversal responses to l-norepinephrine injections but had no effect on the dilator responses to l-epinephrine. It is concluded that, in skeletal muscle, there are three types of vasoreceptors under autonomic control. Two of these, one constrictor and one dilator, are innervated; the third, a dilator receptor, is only under hormonal control.

Effects of pH on Blood Flow and Peripheral Resistance in Muscular and Cutaneous Vascular Beds in the Hind Limb of the Pentobarbitalized Dog

The responses of the vascular beds in skeletal muscle and skin to changes in blood pH on the acid and alkaline sides of the physiologic range were compared. Dilatation occurred in both cutaneous and muscular beds when the blood pH was shifted to the acid range. Dilatation also occurred in the muscle beds when the blood pH was shifted to the alkaline range but such change in blood pH caused vasoconstriction in skin.

Comparison of Changes in Mesenteric Resistance Following Splanchnic Nerve Stimulation with Responses to Epinephrine and Norepinephrine

This is a study of the characteristics of the splanchnic nerve supply to the mesenteric vascular circuit. The flow and pressure responses in the dogs superior mesenteric artery to splanchnic nerve stimulation and to intraarterial injections of epinephrine and norepinephrine, before and during various levels of adrenergic blockade, are analyzed. The results suggest that the splanchnic nerve contains only vasoconstrictor fibers, the mediator of which is probably norepinephrine, but that it also contains fibers which induce the release of epinephrine from the adrenal gland. No evidence for the presence of cholinergic dilator fibers was found.