Mechanisms of cold intolerance in patients with angina.

OBJECTIVES: Patients with angina often report that symptoms are worse in cold weather. This study was designed to determine differences between cold-tolerant and cold-intolerant patients in the hemodynamic and ischemic response to exercise at cold temperatures and to assess the role of catecholamines and baroreceptor function. BACKGROUND: Studies have suggested that the heart rate response may differ at cold temperatures, but the mechanism and role of this variation have not been examined. METHODS: Seven cold-intolerant and seven cold-tolerant patients with angina underwent exercise treadmill testing at 6 and 25 degrees C with measurement of catecholamines. Baroreceptor function was assessed by the decrease in systolic blood pressure after patients stood up from the supine position. RESULTS: Norepinephrine levels increased by 139% in the cold environment, but there were no differences between cold-intolerant and cold-tolerant patients. Consequently, blood pressure was higher in the cold environment in all patients, but the heart rate response was similar. However, cold-intolerant patients had a steeper heart rate response in the cold and developed ischemia (mean [+/- SEM] 201 +/- 58 vs. 242 +/- 50 s, p = 0.05) and angina (348 +/- 87 vs. 449 +/- 60 s, p = 0.04) earlier in the cold environment, a difference not seen in the cold-tolerant patients. Baroreceptor function was impaired in cold-intolerant patients (decrease in systolic blood pressure after patients stood up from the supine position 19 +/- 7 vs. 0 +/- 4 mm Hg, p = 0.04). CONCLUSIONS: Exposure to cold causes an increase in blood pressure with an associated increase in myocardial oxygen demand in all patients. In cold-tolerant patients, this increase may be offset by a reduction in heart rate if baroreceptor function is normal. If baroreceptor function is abnormal, heart rate may not decrease in response to a cold-induced increase in blood pressure. This mechanism may account for some of the variability in tolerance to cold exposure that affects patients with exertional angina.

Disruption of neocortical lamina V neuronal bursts by serotonin in urethane anaesthetized rats.

Time-shared high speed cyclic voltametry using carbon fibre multibarrelled microelectrodes was used to monitor the concentration of 5-Hydroxytryptamine administered by iontophoresis to locations in lamina V of Sm l neocortex and to record spontaneous neuronal spike activity. In the absence of 5-Hydroxytryptamine at any one recording location the firing of two or more individual units was seen to be synchronized so that the pattern of multi-unit activity consisted of synchronized clusters of spike activity interspersed with period of neuronal silence. The repetition rate of such clusters of neuronal activity was seen to be between 0.5 and 4Hz. Maximum concentrations of 2.7 x 10(-7) M 5-Hydroxytryptamine produced by iontophoresis disrupted synchronized neuronal cluster activity. 5-Hydroxytryptamine at a concentration of 6.2 x 10(-8) M resulted in a greater than 50% inhibition of activity for 47 single units but a change in firing pattern from cluster restricted high frequency activity to a continuous mode of firing for a separate population of 11 units. Intraperitoneal administration of P-Chloroamphetamine produced similar changes of neuronal firing and hence loss of synchrony.

Effect of posture on body temperature of young men in cold air.

We studied eight young adult men to see whether a supine posture caused a fall in body core temperature in the cold, as it does in thermoneutral conditions. In air at 31 degrees C (thermoneutral), a supine posture for 3 h reduced mean aural, gastric, oesophageal and rectal temperatures by 0.2-0.4 degree C, compared to upright and increased femoral artery blood flow from 278 (SEM 42)ml.min-1 whilst upright to 437 (SEM 42) ml.min-1 whilst supine. In cold air (8 degrees C) the supine posture failed to reduce these temperatures [corrected] significantly, or to increase femoral blood flow: it reduced heart rate, and increased arterial systolic and pulse pressures adjusted to carotid sinus level, less than in thermoneutral conditions. However, the behaviour of core temperature at the four sites was significantly nonuniform between the two postures in the cold, mainly because the supine posture tended to reduce rectal temperature. It may have done so by reducing heat production in the muscles of the pelvis, since it reduced overall metabolic rate from 105 (SEM 8) to 87 (SEM 4) W.m-2 in the cold. In other respects the results indicated that posture ceased to have an important effect on body core temperatures during cold stress.

Effect of pirenzepine on oesophageal, gastric, and enteric motor function in man.

The effect of pirenzepine on oesophageal, gastric, and enteric motor function was evaluated in six healthy volunteers. Each subject was studied before and after taking pirenzepine, 100 mg/day, for 3 days. Half and complete gastric emptying times of clear liquid, assessed by epigastric impedance, were significantly delayed by the drug: 6.16 +/- 1.74 min and 13.8 +/- 4.64 min versus 16.65 +/- 3.03 min and 25.1 +/- 8.2 min, respectively (p less than 0.05). Enteric motility was assessed by manometry, and variables studied were the duration of the various phases of the migratory motility complex, the frequency of contractions in phase III, and the amplitude of contractions in phases II, III, and in the postprandial period. Only phase I was affected and was significantly prolonged by the drug: 16.08 +/- 5.94 min versus 31.65 +/- 12.88 min (p less than 0.01). Oesophageal motility was assessed by manometry. Variables studied were amplitude and duration of contractions in the body of the oesophagus, and lower oesophageal sphincter pressure. Results were not significantly changed by the drug. We conclude that pirenzepine, given at a dose used for treatment of peptic ulcer disease, significantly delays the gastric emptying of liquids, has minimal effect on enteric motility, and has no effect on oesophageal motility. The effect on gastric emptying may be therapeutically useful by reducing the acid load on the duodenum in duodenal ulcer disease.

Modulation of the duration of human postprandial motor activity by sleep.

We have measured the effect of the presence of food in the gastrointestinal tract on proximal small bowel motility during sleep. Motility was measured in eight healthy ambulant subjects using two strain-gauge microtransducers incorporated in a fine (2.5 mm OD) nasojejunal tube. The subjects ate a 540-cal evening meal (EM) on the first day. On the following day they ate an equicaloric meal (with similar proportion of carbohydrates, proteins, and fats) at lunch time (MM) and then another equicaloric late meal (LM) 15 min before going to bed. All subjects were asleep within 30 min of completing the LM. Postprandial activity was significantly (P less than 0.001) shortened after LM, but there was no difference in the postprandial motor activity after MM and EM. Migrating motor complex (MMC) cycle lengths were similar after MM, EM, and LM. There was no difference in the duration of phase II of the MMC cycle after MM, EM, and LM even though subjects were asleep during the MMC cycles after LM. The MMC propagation velocity after LM and EM was significantly (P less than 0.01, P less than 0.001, respectively) slower than the diurnal MMC propagation velocity after MM. In health, postprandial activity is diminished during sleep, whereas the consumption of a LM restores the phase II activity usually absent during sleep. A LM also abolishes the expected reduction in nocturnal MMC cycle length but maintains the circadian variation in the propagation velocity of the MMC cycle.