Anti-inflammatory effect of high-dose insulin treatment after urgent coronary revascularization surgery.

BACKGROUND: The administration of insulin has been shown to exert cardioprotective and immunomodulatory properties. Ischemia and inflammation are typical features of acute coronary syndrome, thus it was hypothesized that high-dose glucose-insulin-potassium (GIK) treatment could suppress the systemic inflammatory reaction and attenuate myocardial ischemia-reperfusion injury in patients with unstable angina pectoris after urgent coronary artery bypass surgery. METHODS: Forty patients with unstable angina pectoris scheduled for urgent coronary artery bypass surgery and cardiopulmonary bypass were randomly assigned to receive either high-dose insulin treatment (short-acting insulin 1 IU/kg/h with 30% glucose 1.5 ml/kg/h administered separately) or control treatment (saline). Blood glucose levels were targeted to 6.0-8.0 mmol/l in both groups by adjusting the rate of glucose infusion in the GIK group and by additional insulin in the control group as needed. RESULTS: High-dose insulin treatment was associated with significantly lower average C-reactive protein (23.8 vs. 40.1 mg/l, P= 0.008) and free fatty acid levels (0.22 vs. 0.41 mmol/l, P= < 0.001) post-operatively. Average blood glucose levels were comparable during the intensive care unit (ICU) stay (7.1 vs. 6.9 mmol/l, P= 0.5) and 95% of the control patients received supplemental insulin. The pro-inflammatory cytokine response [interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha)] did not differ between the groups and beneficial effects on myocardial injury were not detected. CONCLUSIONS: High-dose insulin treatment has potential anti-inflammatory properties independent of its ability to lower blood glucose levels. Even profound suppression of free fatty acid levels, the attenuation of myocardial ischemia-reperfusion injury was not detected.

Apoptotic activity is increased in brain cortex infarct after hypothermic circulatory arrest in a porcine model.

OBJECTIVE: It has been shown that apoptosis contributes to neuronal cell death after ischemia, and we evaluated the degree of apoptotic activity occurring in brain cortex of pigs after hypothermic circulatory arrest (HCA). DESIGN: Thirty-one pigs underwent 75 min of HCA at 20 degrees C. Histological examination of the brain was performed, and slides of brain cortex were evaluated for apoptotic activity by the TUNEL method. RESULTS: Ten animals died during the first postoperative day and 21 survived until the seventh postoperative day. Brain cortex infarcts were found in animals that survived 7 days and these were included in this study. The median histopathological score among animals that died on the first postoperative day was 3.0 (range, 2-4), whereas it was 4.0 (range, 2-4) among survivors (p = 0.019). The apoptotic index was particularly high in the area of the infarct, whereas only a few TUNEL-stained cells were observed in noninfarcted areas. The apoptotic index was nil in all pigs that died in the first postoperative period, whereas it was 2.0 (range, 0-6) among the animals that survived until the seventh postoperative day (p < 0.0001). CONCLUSION: The apoptotic index was significantly increased in brain cortex infarcts of animals that survived 7 days after HCA, whereas only a few apoptotic cells were observed in noninfarcted areas of these animals as well as in animals that died on the first postoperative day. Further studies are required to elucidate the timing of development of brain infarction after HCA and whether neuroprotective strategies targeting the apoptotic process may mitigate brain damage.

Determinants of mortality after hypothermic circulatory arrest in a chronic porcine model.

OBJECTIVE: Beside neurological morbidity, mortality is a relevant end-point of experimental porcine model of hypothermic circulatory arrest (HCA) and this study was conducted to identify the determinants for postoperative death. METHODS: One hundred and thirty-five pigs underwent a 75-min period of HCA at 20 degrees C to evaluate the efficacy of different methods of cerebral protection. RESULTS: Survival rate at 7-day follow-up was 52%. Lower oxygen extraction, oxygen consumption/kg, and venous lactate at the end of cooling and higher oxygen delivery rates were significantly associated with better outcome. Logistic regression showed that the oxygen consumption/kg at the end of cooling was the only predictor of mortality (P=0.046). Animals with an oxygen consumption/kg rate less than 1.43 ml/min per kg at the end of cooling had a mortality rate of 28%, whereas it was 50% among animals with an oxygen consumption/kg rate higher or equal to 1.43 ml/min per kg (P=0.020). The latter had even an increased 1-day mortality rate (40% vs. 26%) (P not significant). The mortality rate after anesthesia induction with ketamine plus 100% of oxygen was 38%, 45% after anesthesia induction with ketamine plus 35% oxygen, and 53% after anesthesia with medetomidine plus 35% oxygen (P not significant). CONCLUSIONS: Parameters of oxyhemodynamics should be monitored especially from the induction of anesthesia to the end of cooling before a 75-min period of HCA. The use of medetomidine and/or 35% of oxygen at induction of anesthesia should be avoided in favor of ketamine plus 100% of oxygen.

The N-methyl-D-aspartate antagonist memantine has no neuroprotective effect during hypothermic circulatory arrest: a study in the chronic porcine model.

BACKGROUND: Glutamate excitotoxicity has an important role in the development of brain injury after prolonged hypothermic circulatory arrest. The goal of the present study was to determine the potential efficacy of memantine, an N -methyl-D -aspartate receptor antagonist, to mitigate cerebral injury after hypothermic circulatory arrest. METHODS: Twenty pigs (23-33 kg) were randomly assigned to receive memantine (5 mg/kg) or placebo in a blinded fashion before a 75-minute period of hypothermic circulatory arrest at 20 degrees C. Hemodynamic, electroencephalographic, and metabolic monitoring were carried out. The intracerebral concentrations of glucose, lactate, glutamate, and glycerol were measured by means of enzymatic methods on a microdialysis analyzer. Daily behavioral assessment was performed until the animals died or were put to death on day 7. Histologic analysis of the brain was carried out in all animals. RESULTS: In the memantine group, 5 of 10 animals survived 7 days compared with 9 of 10 in the placebo group. The median behavioral score at day 7 was 3.5 in the memantine group and 7.5 in the placebo group (P >.2). Among the surviving animals, medians were 9.0 and 8.0 on day 7 (P >.2), respectively. The medians of recovered electroencephalographic bursts were equal in both groups. The median of total histopathologic score was 16 in the memantine group and 14 in the placebo group (P >.2). There was a negative correlation between glutamate levels and electroencephalographic burst recovery (tau = -0.377, P =.043). A positive correlation was found between the highest individual glutamate value and histopathologic score (tau = 0.336, P =.045). CONCLUSIONS: The present study demonstrates that memantine has no neuroprotective effect after hypothermic circulatory arrest in the pig. In addition, we have shown the accuracy of cerebral glutamate measurements to predict histopathologic injury after hypothermic ischemia.

The role of cerebral microdialysis in predicting the outcome after experimental hypothermic circulatory arrest.

OBJECTIVE: To evaluate whether and which of the cerebral microdialysis parameters are predictive of postoperative outcome after an experimental 75-min period of hypothermic circulatory arrest (HCA) in a chronic porcine model. DESIGN: Seventy-four juvenile female pigs underwent a 75-min period of HCA at 20 degrees C. A microdialysis catheter was placed into the cortex gray matter and brain extracellular concentrations of glucose, lactate, glycerol and glutamate were measured throughout the experiment by enzymatic methods using a microdialysis analyzer. Surviving animals were sacrificed on the 7th postoperative day and histopathological examination of the brain was performed. RESULTS: Brain glucose concentrations were higher in animals that survived (p = 0.017), especially from the 90-min until the 7-h interval after the start of rewarming. The blood venous concentrations of glucose were also higher among survivors, and correlated significantly with the brain glucose levels at 2-h and 4-h intervals after the start of rewarming. Higher concentrations of brain lactate, glycerol and glutamate were observed throughout the study among animals that died postoperatively. Brain glutamate and glycerol concentrations were significantly, negatively correlated with brain glucose concentrations. The lactate/glucose ratio was significantly lower among survivors during the postoperative period (p=0.014). Furthermore, brain glucose concentrations were higher and brain glycerol concentrations lower among the animals that did not develop brain infarction, but such differences did not reach statistical significance. CONCLUSION: Cerebral microdialysis is a useful tool for cerebral monitoring during experimental HCA. Low brain glucose concentrations and high brain lactate/glucose ratios after HCA are strong predictors of postoperative death. Brain glucose concentrations are negatively correlated with brain glycerol and glutamate concentrations.

Leukocyte filtration improves brain protection after a prolonged period of hypothermic circulatory arrest: A study in a chronic porcine model.

BACKGROUND: Ischemic cerebral injury follows a well-attested sequence of events, including 3 phases: depolarization, biochemical cascade, and reperfusion injury. Leukocyte infiltration and cytokine-mediated inflammatory reaction are known to play a pivotal role in the reperfusion phase. These events exacerbate the brain injury by impairing the normal microvascular perfusion and through the release of cytotoxic enzymes. The aim of the present study was to determine whether a leukocyte-depleting filter (LeukoGuard LG6, Pall Biomedical, Portsmouth, United Kingdom) could improve the cerebral outcome after hypothermic circulatory arrest. METHODS: Twenty pigs (23-30 kg) were randomly assigned to undergo cardiopulmonary bypass with or without a leukocyte-depleting filter before and after a 75-minute period of hypothermic circulatory arrest at 20 degrees C. Electroencephalographic recovery, S-100beta protein levels, and cytokine levels (interleukin 1beta, interleukin 8, and tumor necrosis factor alpha) were recorded up to the first postoperative day. Postoperatively, all animals were evaluated daily until death or until electively being put to death on day 7 by using a quantitative behavioral score. A postmortem histologic analysis of the brain was carried out on all animals. RESULTS: The rate of mortality was 2 of 10 in the leukocyte-depletion group and 5 of 10 in control animals. The risk for early death in control animals was 2.5 (95% confidence interval, 0.63-10.0) times higher than that of the leukocyte-depleted animals. The median behavioral score at day 7 was higher in the leukocyte-depletion group (8.5 vs 3.5; P =.04). The median of total histopathologic score was 8.5 in the leukocyte-depletion group and 15.5 in the control group (P =.005). CONCLUSION: A leukocyte-depleting filter improves brain protection after a prolonged period of hypothermic circulatory arrest.

Slow vasomotor fluctuation in fMRI of anesthetized child brain.

Signal intensity changes in fMRI during rest caused by vasomotor fluctuations were investigated in this work. Resting-state baseline fluctuations were evaluated in 12 children anesthetized with thiopental. Five subjects had fluctuations related to subvoxel motion. In seven subjects without significant motion, slow signal fluctuation at 0.025-0.041 Hz near one or more primary sensory cortices was observed. In each subject the amplitude and frequency of the fluctuations were stable. It is hypothesized that thiopental, which reduces blood pressure and flow in the cortex, alters the feedback in neurovascular coupling leading to an increase in the magnitude and a reduction in the frequency of these fluctuations. The use of anesthesia in fMRI may provide new insight into neural connectivity and the coupling of blood flow and neural metabolism.

Lamotrigine improves cerebral outcome after hypothermic circulatory arrest: a study in a chronic porcine model.

BACKGROUND: Glutamate excitotoxicity has an important role in the development of brain injury after prolonged hypothermic circulatory arrest. The goal of the present studies was to determine the potential efficacy of lamotrigine, an Na(+) channel blocker, to mitigate cerebral injury after hypothermic circulatory arrest. METHODS: Sixteen pigs (21-27 kg) were randomly assigned to receive lamotrigine (20 mg/kg) or placebo in a blinded fashion before a 75-minute period of hypothermic circulatory arrest (20 degrees C). Hemodynamic, electroencephalographic, and metabolic monitoring were carried out. S-100beta protein was determined up to the first postoperative morning. Daily behavioral assessment was performed until the animal died or was put to death on day 7. Histologic analysis of the brain was carried out in all animals. RESULTS: Complete behavioral recovery was seen in 5 of 8 (63%) animals after lamotrigine administration, compared with 1 of 8 (13%) in the placebo group (P =.02). Among the animals that survived for 7 days, the median behavioral score was higher in the lamotrigine group (8 vs 7, P =.02). The medians of recovered electroencephalographic bursts in the lamotrigine group were higher than those in the placebo group 4 1/2 hours after the start of rewarming (P =.01). The median S-100beta level was lower in the lamotrigine group (0.01 microg/L) than in placebo controls (0.1 microg/L) 20 hours after the start of rewarming (P =.01). The median of total histopathologic score was 5.5 in the lamotrigine group and 7.5 in the placebo group (P =.06). CONCLUSIONS: The present data suggest that lamotrigine improves neurologic outcome after a prolonged period of hypothermic circulatory arrest.

Intermittent retrograde cerebral perfusion during prolonged period of hypothermic circulatory arrest: a study in a chronic porcine model.

Previous studies have shown that although retrograde cerebral perfusion (RCP) improves cerebral outcome during hypothermic circulatory arrest (HCA), RCP exposes the brain to subsequent edema. In this study, we have compared intermittent RCP (I-RCP) with continuous RCP (C-RCP) and HCA alone to determine whether the rate of fluid sequestration can be decreased without losing the beneficial effects of RCP. Eighteen pigs were randomly assigned to undergo 75 min of I-RCP, C-RCP or HCA at 20 degrees C. Hemodynamic and metabolic measurements were carried out for upto 20 h. Behavioral assessments were examined until day 7, when histopathologic analysis of the brain was performed. The median amount of fluid sequestered was 145 ml after C-RCP and -50 ml after I-RCP (p = 0.04). The mean brain weight of the animals that died within the first postoperative day was significantly higher than that in electively sacrificed animals in the C-RCP group (p = 0.04). These data suggest that if RCP is implemented intermittently, the rate of cerebral edema can be decreased, without compromising the benefits of this strategy.

Serum S-100beta protein predicts brain injury after hypothermic circulatory arrest in pigs.

OBJECTIVE: Serum S-100beta protein is suggested to be a neurobiochemical marker of brain injury after cardiac and aortic arch surgery. The aim of the present study was to investigate the predictive value of S-100beta protein with respect to histopathological analysis of the brain after a prolonged period of hypothermic circulatory arrest (HCA). METHODS: Eighteen pigs (21 to 31 kg) underwent a 75 min period of HCA at 20 degrees C. Serum concentrations of S-100beta were assayed in mixed venous blood before and 2, 4, 7 and 20 h after HCA. A semiquantitative post-mortem histopathological analysis scoring all main regions of the brain was carried out in every animal. RESULTS: All animals were stable during and after cardiopulmonary bypass (CPB) and survived at least to the first postoperative day. Ten of the 18 animals survived 7 days after surgery and were electively sacrificed. Animals with severe histopathological injury showed higher serum S-100beta protein levels at every time point after HCA. The strongest correlation between the total histopathologic score and serum S-100beta levels was found at 7 h after HCA (tau = 0.422 and p = 0.023). CONCLUSION: Serum S-100beta protein levels correlate with histopathological injury after a prolonged period of HCA in pigs. This finding supports the results of previous studies suggesting the potential accuracy of S-100beta in the prediction of brain injury after cardiac surgery.

Is routine ipsilateral adrenalectomy during radical nephrectomy harmful for the patient?

To investigate the effects of unilateral adrenalectomy on the postoperative course and laboratory parameters, 40 patients with a renal tumour were randomized either to undergo (n = 20) or not to undergo (n = 20) ipsilateral adrenalectomy. Adrenal hormone (cortisol, epinephrine, norepinephrine and aldosterone), adrenocorticotropic hormone, electrolyte, creatinine, growth hormone, glucose, insulin and free fatty acid concentrations were measured preoperatively and postoperatively. Cortisol and epinephrine concentrations were elevated immediately after the operation but returned to preoperative levels within the first 2 postoperative days. There were no significant differences between the adrenalectomy and non-adrenalectomy groups, except that the cortisol concentration was higher in the latter in the afternoon of the day of surgery. The conclusion is that no long-term shortage of adrenal hormones is caused by unilateral adrenalectomy. Other metabolic and endocrine responses were identical in the groups. Thus ipsilateral adrenalectomy does not seem to be harmful to the patient and the need for it must be resolved on the basis of local tumour factors.

Atrial plasma ANP and NH2-terminal proANP during right atrial pressure increase in humans.

To compare plasma NT-proANP, a stable and biologically inactive N-terminal portion of ANP prohormone, with the known plasma ANP response to increased right atrial pressure a Swan-Ganz catheter was inserted into the right atrium of five normal healthy male volunteers. The elevation of right atrial pressure was produced by a head-down tilt after a hypertonic saline infusion. Blood samples were drawn from the lumen of the right atrium. After 5 min of starting the tilt the right atrial pressure had increased from 7.0 +/- 1.0 to 11.6 +/- 0.9 mmHg (P < 0.05) and then began to normalize in spite of the constant tile. Atrial plasma ANP increased in relation to the pressure increase and peaked at 15 min after the start of the tilt. The change was from 27.9 +/- 6.5 to 53.9 +/- 9.7 pmol L-1 (P < 0.05). Atrial plasma NT-proANP increased significantly from 357 +/- 91.2 to 529.1 +/- 116.0 pmol L-1 (P < 0.05) at 10 min and remained high throughout the experiment. The molar ratio of NT-proANP to ANP varied in atrial plasma from 9.5 +/- 1.2 to 13.9 +/- 2.7 showing that the plasma clearance of ANP from plasma was much higher than that of NT-proANP.

0.1% bupivacaine does not reduce the requirement for epidural fentanyl infusion after major abdominal surgery.

BACKGROUND AND OBJECTIVES: Although local anesthesia has been demonstrated to potentiate spinal morphine analgesia in animal studies, results comparing epidural local anesthesia/opioid mixtures with opioid alone are contradictory in clinical studies. The hypothesis was that, although the concentration of bupivacaine (0.1%) was low to minimize its adverse effects, if the infusion rate of a fentanyl/bupivacaine solution was closely adjusted according to need, the presence bupivacaine would reduce the requirement for epidural fentanyl. METHODS: Forty patients were randomly assigned to receive either fentanyl (10 micrograms/mL) or a fentanyl/bupivacaine (0.1%) mixture epidurally corresponding to the dermatome of the surgical incision in a double-blind fashion for the first 18 hours after major abdominal surgery. The infusion was titrated for each patient to the rate required for pain relief during forced inspiration (pain score < or = 2, maximum 10). Pain scores, the fentanyl doses required, plasma concentrations of fentanyl at 18 hours, and the incidence and severity of adverse effects were recorded. RESULTS: Patients reported similar median pain scores and were equally satisfied with pain relief in both groups. The mean required post-operative fentanyl infusion rate (57.7 +/- 19.5 micrograms/h) and the plasma concentrations (0.84 +/- 0.36 ng/mL) in the fentanyl group were comparable to the infusion rate (54.4 +/- 19.2 micrograms/h) and the plasma concentrations (0.86 +/- 0.36 ng/mL) in the fentanyl/bupivacaine group. Respiratory and cardiovascular functions were preserved, and the incidence of nausea, pruritus, and periods of drowsiness or sleep were similar in both groups. CONCLUSIONS: In low concentrations (0.1%), bupivacaine did not reduce the titrated dose of epidural fentanyl required for adequate pain relief during forced inspiration after major abdominal surgery. The incidence and severity of adverse effects were also comparable whether or not low-dose bupivacaine infusion was used.

A clinical and pharmacokinetic comparison of ropivacaine and bupivacaine in axillary plexus block.

The clinical and pharmacokinetic properties of ropivacaine and bupivacaine, both 5 mg/mL, used in axillary plexus block were compared in 60 patients in this randomized, double-blind, parallel-group study. The axillary plexus was identified with a nerve stimulator and 30, 35, or 40 mL of drug, depending on body weight, was injected into the perivascular sheath. In 20 patients, venous blood samples for the pharmacokinetic measurement were obtained over 24 h. The median onset times for anesthesia and complete motor block were in the range of 12-48 min and 5-20 min, respectively. Thirty-eight percent of patients in the ropivacaine group and 29% in the bupivacaine group needed additional nerve block(s) or supplementary analgesia and 7% in the bupivacaine group needed general anesthesia for surgery. Anesthesia was achieved in 52%-86% of the evaluated six nerves in the ropivacaine group and in 36%-87% in the bupivacaine group; the lowest figures were seen in the musculocutaneous nerve. In the pharmacokinetic study the mean peak plasma concentrations (Cmax) were 1.28 +/- 0.21 mg/L in the ropivacaine group and 1.28 +/- 0.47 mg/L in the bupivacaine group and the median times to peak plasma concentration (tmax) were 0.86 h and 0.96 h, respectively. The median terminal half-lives (t1/2) were 7.1 h and 11.5 h in the ropivacaine group and the bupivacaine group, respectively (P = 0.07). No statistically significant differences were found between ropivacaine and bupivacaine in either the clinical or the pharmacokinetic comparisons.

Plasma ANP during hypertonic NaCl infusion in man.

To determine the relationship between hyperosmolality and immunoreactive atrial natriuretic peptide of heart atrial plasma six healthy men were given 0.06 ml kg-1 min-1 855 mmol l-1 NaCl, i.v., for 2 h. The right atrial pressure and atrial plasma atrial natriuretic peptide were measured. During the infusion, right atrial pressure was kept constant by lowering the legs of the subject in a supine position downwards if any increase in the pressure was seen. There was a significant and linear increase in atrial serum osmolality, from 288 +/- 3.3 to 307 +/- 3.2 mOsm kg-1 (P less than 0.001). No statistically significant changes in right atrial pressure were seen. Regression analysis revealed that there was a statistically significant correlation between serum osmolality and plasma ANP in three subjects (responders) (r2: 0.5241, 0.8965, 0.6695). In three other subjects (nonresponders), there was no correlation between osmolality and ANP. The mean basal osmolality of responders was 280 mOsm kg-1 and the mean basal osmolality of nonresponders was 295 mOsm kg-1. In contrast, all subjects responded with an increase in plasma ANP (P less than 0.05) after RAP had been increased by tilting the legs of the subject upwards for 30 min. We conclude that the right atrial pressure regulates the release of atrial natriuretic peptide. Serum hyperosmolality may also contribute to the regulation of atrial natriuretic peptide independently of the right atrial pressure in man.

Less peri- and postoperative inotropic support in open-heart patients with vasomotor waves during cardiopulmonary bypass?

Although vasomotor waves (VMW) (Mayer waves) were recognized more than one century ago their physiological role is still under discussion. During cardiopulmonary bypass (CPB) the appearance of VMW is random. The clinical significance of the phenomenon was studied by comparing open-heart patients with (n = 33) or without (n = 33) VMW of arterial pressure during CPB. The patients with VMW had higher perfusion pressure (p less than 0.05) and vascular resistance (p less than 0.01) during bypass and higher mean arterial pressure before and after CPB. During CPB the need for vasoconstrictors was of lesser magnitude (p less than 0.01) but the need for vasodilators was of greater magnitude (p less than 0.001) in patients with VMW and they also less frequently needed inotropic support at weaning from CPB (p less than 0.05) or after CPB (p less than 0.01). The use of inotropics was also shorter (p less than 0.01) during intensive care in the patients with VMW. Based on the present results the open-heart patients who had VMW during CPB appeared to have higher arterial blood pressure and to need less pharmacological cardiovascular support during the intraoperative and the immediate postoperative period.

Spontaneous oscillation of systemic arterial pressure during cardiopulmonary bypass in the dog.

Cardiopulmonary bypass and an open-heart operation were carried out on four beagle dogs kept under ketamine anesthesia. Oscillation of systemic arterial pressure during this maneuver was observed in three dogs and oscillation of pulmonary arterial pressure in two dogs. Mean amplitude of the oscillation in systemic arterial pressure was 6 to 7 mm Hg and that in pulmonary arterial pressure about 1 mm Hg. The duration of an oscillatory wave was about 20 s. Systemic arterial pressure was 130 to 150 mm Hg. The oscillation disappeared in two dogs when weaning from the bypass. These oscillations resemble those observed in humans during cardiopulmonary bypass and also those observed in experimental animals without bypass conditions.

Spontaneous oscillation of the systemic arterial pressure during cardiopulmonary bypass in man. The effects of some drugs used during the operation.

Despite the fact that the blood flow maintained during cardiopulmonary bypass is rather steady in the extracorporeal pump output, the arterial pressure under high-dose fentanyl anaesthesia quite often shows sinusoidal oscillations. In the present study the duration of an oscillatory cycle was on average 17.6 +/- 3.6 s, its amplitude 7.3 +/- 1.6 mm Hg and mean systemic arterial pressure 75 +/- 12 mm Hg. The oscillation is affected by the drugs used under bypass conditions. In our series of clinical observations the blood pressure oscillation disappeared under the influence of chlorpromazine, phentolamine, droperidol, and enflurane, and it disappeared or at least was distinctly attenuated under fentanyl, thiopental, diazepam, sodium nitroprusside, nitroglycerin, acebutolol, and potassium chloride. Pancuronium, atropine and furosemide appeared to be practically ineffective. In spite of the fact that the drugs used affected several sites of the sympathetic efferent chain, the disappearance and attenuation of the oscillation were associated with a simultaneous decrease of blood pressure. Hence, it is suggested that the occurrence of the oscillations requires some level of peripheral vascular tone.

Spontaneous oscillations of systemic arterial pressure during cardiopulmonary bypass in man.

Extracorporeal blood circulation (ECC) provides a steady flow and minimal pulmonary circulation in the absence of cardiac function. Oscillations of systemic arterial pressure were observed in 70 patients during ECC. At the onset of oscillations the frequency was as a rule 4 cycles per minute but depended on the temperature and showed a positive correlation with it. Correspondingly, the amplitude was about 6 mm Hg and depended on aortic pressure and showed a positive correlation with it. During the cooling phase of ECC the frequency decreased and the amplitude increased. The oscillations were independent of central venous pressure and ventilation. The oscillations disappeared either at the beginning of restitution of cardiac function or with decreasing arterial pressure caused by drug administration or rewarming. Arterial blood pressure oscillations have been described in experimental animals under various conditions but also in conscious man. The mechanisms underlying these oscillations are suggested to be nervous in origin, as is possible also in the present findings.