Post-carotid endarterectomy hypertension: association with elevated cranial norepinephrine

The cause and mechanism of post-carotid endarterectomy hypertension remains unknown. To determine the influence of the sympathetic and renin-angiotensin system, we measured cranial and peripheral plasma levels of catecholamine and renin in patients undergoing carotid endarterectomy. Baseline samples were drawn just before carotid clamping (sample I) and compared with study samples drawn immediately after clamp release (sample II), 2 to 6 hours after surgery (sample III), and then 18 to 24 hours after surgery (sample IV). The patients with post-carotid endarterectomy hypertension had an associated increase of cranial and peripheral norepinephrine levels in the postoperative hypertensive period whereas the patients without post-carotid endarterectomy hypertension did not. This association was most pronounced and statistically significant in cranial samples II (p = 0.032) and III (p = 0.005). Epinephrine and dopamine values did not correlate with post-carotid endarterectomy hypertension. Renin values were higher in cranial than in peripheral samples at time period 2 (p = 0.011), suggestive of a central nervous system Goldblatt phenomenon. However, the renin values did not correlate with post-carotid endarterectomy hypertension. We conclude that post-carotid endarterectomy hypertension is associated with elevated cranial norepinephrine levels, suggestive of a central nervous system sympathomimetic mechanism. Optimal prevention and treatment of this brief but frequently occurring hypertension should include a central-acting sympatholytic agent.     

High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer's disease brain.

The mitochondrial theory of aging proposes that mitochondrial DNA (mtDNA) accumulates mutations with age, and that these mutations contribute to physiological decline in aging and degenerative diseases. Although a great deal of indirect evidence supports this hypothesis, the aggregate burden of mtDNA mutations, particularly point mutations, has not been systematically quantified in aging or neurodegenerative disorders. Therefore, we directly assessed the aggregate burden of brain mtDNA point mutations in 17 subjects with Alzheimer's disease (AD), 10 elderly control subjects and 14 younger control subjects, using a PCR-cloning-sequencing strategy. We found that brain mtDNA from elderly subjects had a higher aggregate burden of mutations than brain mtDNA from younger subjects. The average aggregate mutational burden in elderly subjects was 2 x 10(-4) mutations/bp. The bulk of these mutations were individually rare point mutations, 60% of which changed an amino acid. Control experiments ensure that these results were not due to artifacts arising from PCR error, mistaken identification of nuclear pseudogenes or ex vivo oxidation. Cytochrome oxidase activity correlated negatively with increasing mutational burden. These findings significantly bolster the mitochondrial theory of aging.     

Effect of continuous postoperative epidural analgesia on intestinal motility

The effect of postoperative epidural bupivacaine on intestinal motility was studied by measuring the transit time of barium contrast through the intestines in 16 patients after resection of the left colon and/or rectum. Fourteen patients served as controls and received postoperative injections of pentazocine. Mean transit time through the intestinal tract was 35 h in the epidural group and 150 h in the control group, a difference that is significant at the 0.1 per cent level. The average time before passage of flatus and faeces was different between the two groups at the 0.1 per cent level. We conclude that postoperative epidural bupivacaine constitutes an effective means of analgesia after colorectal surgery and is associated with a short duration of intestinal paralysis.     

Effect of verapamil on ventilatory and circulatory responses to hypoxia and hypercapnia in normal subjects.

Recent investigations have shown that the calcium channel blocker verapamil attenuated the hypoxic ventilatory chemosensitivity of carotid body in animals. To determine whether this is also the case in humans, transient physiological chemodenervation by O2 breaths (withdrawal test) during sustained hypoxia (N = 7), and ventilatory and circulatory responses to progressive hypoxia and hypercapnia (N = 8) were examined after oral administration of verapamil. During sustained hypoxia after verpamil, there was a significant reduction of withdrawal response from 5th to 25th min value (p < 0.01), but not after placebo. On the other hand, no significant difference in ventilatory responses to progressive hypoxia and hypercapnia was observed after verapamil. Verapamil run reveals similar features with placebo run in circulatory parameters except blood pressure response, which tended to be suppressed by verapamil. We conclude that verapamil attenuates peripheral chemoreceptor activity with time during sustained mild hypoxia in normal adult humans and this may be explained by delayed depletion in intracellular Ca2+ for chemotransduction of the peripheral chemoreceptors.