Human cardiovascular evolution and intracranial saccular aneurysms: an hypothesis.

Current predominant theories for the pathogenesis of intracranial saccular aneurysms have a congenital or a degenerative basis. Complementing these theories, the predilection of intracranial aneurysms for the human species has been attributed to a variety of human neurovascular morphological traits, which however, on closer scrutiny are not unique to the human species. Human evolution to a bipedal primate has required significant adaptation in several organ systems, with significant consequent biological costs. We hypothesize that susceptibility to intracranial aneurysms is part of this latter cost of adopting an upright stance with respect to the neurovascular systems. Evidence supporting the above hypothesis, is presented.

Mammalian cardiovascular morphology and the maintenance of cerebral function at high Gz.

The persistence of consciousness at low cerebral perfusion pressures during exposure to high sustained G force in a head-to-foot direction (+Gz), is the rule. Concomitant changes in cerebrospinal fluid and cerebral venous dynamics together with cerebral autoregulation have been proposed to explain this preservation of cerebral function at high Gz. The non-uniform distensibility of the mammalian aortic distributing system plays a fundamental role in maintaining optimal cardiac energy exchange. Morphological evidence is presented suggesting that such a non-uniformity probably extends cranially as well as caudally in man. One consequence of such a cranial extension would be the amplification of the arterial pressure waves to the brain, with the potential for significant pulsatile flow at relatively low mean arterial blood pressures. Such phenomena would result from fundamental design properties of the mammalian cardiovascular system, would not be detected by conventional invasive pressure monitoring, and would serve as a mechanism to maintain optimal cerebral perfusion under condition of increasing +Gz.

Characteristics of arterial myosin in experimental renal hypertension in the dog.

We compared myosin samples isolated from iliac-femoral arteries of control and renal (stenosis) hypertensive dogs to determine the effects of increased blood pressure on the characteristics of the myosin. The ratio of 204-kd (SM-1) to 200-kd (SM-2) myosin heavy chains was approximately 1:0.75 for myosin from the iliac-femoral artery of normotensive dogs. This was not altered significantly in response to hypertension. Both SM-1 and SM-2 myosin heavy chains cross-reacted with antibody against smooth muscle myosin on Western blot analysis. In addition to these heavy chains, purified myosin from both groups showed a very faint protein band slightly below the 200-kd myosin heavy chain on electrophoresis on a highly porous sodium dodecyl sulfate-polyacrylamide gel. This protein band cross-reacted with antibody against nonmuscle myosin but not with smooth muscle myosin antibody. The 20- and 17-kd light chains of myosin isolated from normotensive and hypertensive dogs gave similar results on isoelectric focusing. Peptide maps of tryptic digests of heavy chains revealed both quantitative and qualitative differences. The Ca(2+)-activated myosin ATPase activity measured in high salt (0.5 mol/L KCl) was similar for myosin from both groups, whereas the potassium (ethylenedinitrilo)tetraacetic acid-stimulated ATPase of myosin from hypertensive animals was higher than that from normotensive animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular stability with rapid intravenous infusion of ondansetron.

The acute cardiovascular effects of rapid iv administration of the antiemetic ondansetron, a selective serotonin (5-HT3) receptor antagonist were determined in a randomized, blinded, placebo-controlled study. Measurements of heart rate, blood pressure, oxygen saturation and respiratory rate were made preoperatively over a five-minute period which followed a two-minute infusion of the medication. Intraoperative and postoperative data were not collected. None of the variables recorded changed significantly during the infusion or in the observation period which followed. Within the limitations of this study, we detected no cardiovascular change in the five minutes between the end of the drug infusion and the induction of anaesthesia.

Unregulated self-medication in an ambulatory surgery population.

The objective of this study was to determine whether unregulated self-medication in an ambulatory surgery population was a significant problem in terms of the incidence and nature of drugs detected. We asked 67 consecutive patients who presented for elective ambulatory surgery at a university medical center to volunteer for serum and urine testing with the assurance of confidentiality. All patients denied nonprescription drug use. Initial testing was for amphetamines, barbiturates, benzodiazepines, cocaine, opiates, phencyclidine (PCP), tetrahydrocannabinol (THC) and alcohol. Of the 64 patients who agreed to be tested, 16 patients tested positive for at least one of the above substances; 4 patients demonstrated residua of 2 or 3 substances. No distinctive characteristic of those with evidence of drug use could be identified. We believe that the 25% of patients who tested positive in this group is a conservative estimate of possible unrecognized drug use. We have demonstrated a significant incidence of substance abuse in the ambulatory surgery environment. These findings have serious safety implications, and a higher awareness of possible nonprescription drug use in this environment is needed in medical and support personnel.

Contribution of skeletal muscle activity to the natural history of acceleration-induced loss of consciousness (G-LOC).

G-LOC and the ensuing incapacitation represents an ever present threat to modern fighter aircraft and aviators. Of the techniques developed to combat gravitational induced stress, particularly such stress acting along the head to foot axis (+Gz), a variety of straining maneuvers have assumed prominence. All the latter techniques involve voluntary skeletal muscle tensing to a varying degree. It is hypothesized that the basis for the importance of skeletal muscle activity in improving G tolerance predominantly lies in the increased muscle spindle afferent activity to the reticular activating system. It is also hypothesized that the natural history of G-LOC can be significantly improved by supplementing muscle spindle activity via active and passive skeletal muscle activity.

Altered agonist-activated 86Rb+ efflux from arteries in canine renal hypertension.

Basal rate constants for 86Rb+ efflux from renal arteries of renal hypertensive dogs were lower than those of control animals whereas no differences were found for coronary arteries. Norepinephrine produced parallel increases in efflux rate constants for hypertensive and control renal arteries, but serotonin produced smaller responses in hypertensive compared to control coronary arteries.

Effects of hypertension and its reversal on canine arterial wall properties.

Segments of carotid, femoral, saphenous, and left circumflex coronary arteries were obtained from control, renal hypertensive, and nephrectomized hypertensive dogs for in vitro study of mechanical properties. Hypertension was produced in two-kidney dogs by unilateral renal artery constriction. After 3 months, the compromised kidney was removed in half of the dogs. Mean arterial pressure was significantly elevated in the hypertensive dogs after 3 months (127 +/- 2 vs 94 +/- 1 mm Hg for controls) and partially returned toward normal 3 months after nephrectomy (105 +/- 2 mm Hg). Pressure-diameter relations were determined under conditions of maximum active and passive smooth muscle activation. Contiguous segments were used for the determination of water and connective tissue content. Hypertension was associated with increased passive arterial wall stiffness at most sites, with a partial return toward normal after nephrectomy. Maximum responses to smooth muscle activation (active stress and constriction response) were augmented in arteries from hypertensive dogs and partially returned toward normal in the nephrectomized hypertensive group. The elastin content of these arteries was unchanged, while collagen content was nonuniformly decreased in renal hypertensive dogs. Small decreases were found in the radius-wall thickness ratio of some arteries. No significant mechanical changes occurred in the saphenous artery. The largest hypertension-related changes were found in the coronary arteries, which also exhibited the smallest recovery toward normal properties after nephrectomy. Considerable regional variability of changes in arterial wall in renal hypertensive and nephrectomized hypertensive dogs was found. Incomplete resolution of the hypertension and arterial wall changes by nephrectomy was found in this animal model.

Cardiovascular baroreceptor control during angiotensin-induced acute hypertension in the dog.

Central and regional cardiovascular responses to step changes in carotid sinus pressure were evaluated in dogs before and after increasing carotid sinus reflex set point pressure, by approximately 30%, via an intravenous infusion of angiotensin II at three anesthetic levels (isoflurane). With respect to overall cardiovascular behavior, angiotensin inhibited both the interaction of carotid sinus baroreceptor stimulation and anesthesia upon mean arterial pressure and total resistance, together with the inverse relationship between iliac resistance and carotid sinus pressure. At the set point pressure of the carotid sinus reflex, angiotensin increased set point levels of aortic, celiac, mesenteric and renal resistances, reduced corresponding set point flows, and increased the range of arterial pressure control together with the maximum capacity of the carotid sinus reflex to increase mean aortic pressure and power for all anesthetic levels. Angiotensin increased the set point sensitivity of mean arterial pressure (gain), heart rate, iliac blood flow, aortic, celiac, mesenteric and renal resistance, to changes in carotid sinus pressure for intermediate anesthetic levels. While reflex gain was unchanged by angiotensin, peak gain was significantly increased at lower anesthetic levels. The maximum capacity of the carotid sinus reflex to decrease mean aortic pressure and power was reduced. Thus, intravenous angiotensin infusion producing moderate increases in mean arterial pressure facilitates the ability of the carotid sinus baroreceptors to control mean arterial pressure and heart rate, and results in an increased overall vasoconstrictor capacity. Corresponding increased ability to control regional blood flow was confined to the iliac bed.

Baroreceptor control of central and regional hemodynamics with isoflurane in the dog.

Central and regional hemodynamics were studied at five levels of carotid sinus baroreceptor stimulation and three isoflurane levels. Apart from iliac blood flow, all regional blood flows, together with mean aortic pressure, power and flow decreased in response to an increasing anesthetic level and/or carotid sinus baroreceptor stimulation. These effects were additive with no significant interaction between the two experimental factors. At the carotid sinus reflex set point pressure, isoflurane attenuated the ability of carotid sinus baroreceptors to change mean aortic pressure and power together with the maximum capacity of the carotid sinus baroreceptors to produce vasoconstriction. The maximum capacity of the carotid sinus baroreceptors to produce vasodilation was unaffected by isoflurane. Vagotomy only modified hemodynamic set point values at low isoflurane levels, increasing regional resistances at the expense of flow except for the iliac bed. Following vagotomy, reflex gain was increased as was the maximum capacity of the cardiovascular system to vasoconstrict and vasodilate in response to carotid sinus pressure stimulation, together with the range of arterial pressure control.

Connective tissue analysis of the canine circle of Willis in hypertension.

The collagen and elastin contents of the major arterial components of the canine circle of Willis (basilar artery, posterior cerebral artery, internal carotid artery, middle cerebral artery, and anterior cerebral artery) were determined as measures of the passive mechanical properties of these vessels. Studies were carried out in seven normotensive dogs and seven dogs in which experimental renal hypertension of 3 months duration had been induced. In the normotensive animals, the collagen content of the middle cerebral artery exceeded that of the other vessels considered. The elastin content and the total connective tissue were not significantly affected by arterial site. The middle cerebral artery collagen to elastin ratio was greater than corresponding values for the basilar, posterior cerebral, and internal carotid arteries. Connective tissue differences were less pronounced in the hypertensive animals. No component of the canine circle of Willis in the hypertensive dogs showed a significantly different collagen content, elastin content, total connective tissue content, or collagen to elastin ratio. In comparing cerebral vessels from normotensive and hypertensive dogs, total connective tissue values were greater in hypertension for all arterial sites considered. These acute physiological changes in connective tissue content over small distances in intracranial blood vessels from normotensive animals, together with unique connective tissue responses of these vessels to short term hypertension, may suggest additional possible factors important in the natural history of cerebrovascular pathological conditions.

Effects of angioplasty upon carotid sinus mechanical properties and blood pressure control in the dog.

The effects of vein patch angioplasty of the carotid sinus upon carotid sinus control of blood pressure and carotid sinus mechanical properties were studied in nine vagotomized dogs. Pressures in the isolated carotid sinuses were increased from 60 to 180 mm Hg in steps of 30 mm Hg, and the resulting reflex changes in mean aortic pressure were measured both before and after unilateral angioplasty. Angioplasty significantly decreased aortic pressure for carotid sinus pressures above 60 mm Hg, decreased the calculated carotid sinus reflex set point pressure, and increased the range of control of arterial blood pressure together with the maximal capacity of the arterial baroreceptors to effect vasoconstriction. In five dogs, concomitant changes in carotid sinus diameter were measured. From the latter, together with accompanying changes in sinus wall geometry, were calculated the tension-strain modulus of elasticity of the carotid sinus wall, together with the radial displacement of the media-adventitial junction. Calculated increases in the latter were consistent with the observed increased effectiveness of the carotid sinus baroreceptors after angioplasty. It was concluded that the modification of blood pressure and its control was predominantly due to the surgical exaggeration of normal carotid sinus geometry accompanied by modest changes in carotid sinus wall mechanical properties.

Baroreceptor control of heart rate in chickens (Gallus domesticus).

The baroreceptor control of heart rate was examined in nonanesthetized, nonrestrained, White Leghorn chickens (n = 10) by measuring the heart period response to modest increases in systolic blood pressure induced by IV boluses of phenylephrine (0.04 micrograms/g). In each animal, a sciatic artery and a femoral vein were chronically instrumented for the measurement of blood pressure and heart rate, together with venous access. Sustained and consistent cardiac slowing was seen in all chickens in response to small increases in systolic pressure. The mean slope of the regression equation between heart period and systolic pressure was 13.9 +/- 0.8 s X 10(-4)/mm of Hg. This sensitivity was reduced to 2.1 +/- 1.5 s X 10(-4)/mm of Hg by anesthetizing the chickens with isoflurane (inspired concentrations of 1%).