Myocardial metabolism and adaptation during extreme hemodilution in humans after coronary revascularization.

OBJECTIVE: This study was designed to evaluate the oxygen transport adjustments and myocardial metabolic adaptation that occurs with different levels of hemodilution during normothermia after cardiopulmonary bypass. DESIGN: Prospective, nonrandomized study. SETTING: Operating room in a university hospital. PATIENTS: Eight patients with ejection fractions (> 40%) undergoing elective coronary artery bypass grafting. METHODS: Before the institution of cardiopulmonary bypass, blood was withdrawn from patients to a target hematocrit of 15%. After coronary artery bypass grafting, a catheter was inserted directly into the coronary sinus. After the patients were rewarmed to 37 degrees C, they were weaned from cardiopulmonary bypass. Hemodynamic indices were measured, as well as measurements of myocardial oxygen consumption (VO2) and myocardial metabolism (lactate extraction and coronary sinus hypoxanthine). Measurements were made at three different hematocrit values: 15%, 20%, and 25%. Hematocrit was increased by autologous blood transfusion. MEASUREMENTS AND MAIN RESULTS: The three levels of hemodilution (hematocrit: 17.4 +/- 3.4%; 23.0 +/- 3.7%; 27.8 +/- 4.8%) were significantly different from baseline (hematocrit 37 +/- 2.6%; p < .05). Oxygen delivery, which increased with autologous transfusion, exceeded 350 mL/min/m2 at each level of dilution. The myocardial VO2 increased significantly after autologous transfusion compared with the most dilute condition (7.0 +/- 3.7 mL/min at hematocrit 17.4% vs. 11.2 +/- 4.8 mL/min at hematocrit 23.0% and 12.4 +/- 4.0 mL/min at hematocrit 27.8%). This transfusion-induced increase was also true of myocardial oxygen extraction. Lactate extraction and hypoxanthine release were normal and unchanged at each level of hemodilution. Systemic oxygen extraction ratio increased with hemodilution and decreased with autologous transfusion. CONCLUSIONS: Hemodilution to a hematocrit of approximately 15% is tolerated in anesthetized humans after coronary artery bypass surgery. There was no evidence of myocardial ischemia, as demonstrated by absence of S-T depression on the electrocardiogram, lactate extraction, or hypoxanthine release. In selected patients, postoperative transfusion may be based on systemic physiologic end-points, such as oxygen extraction ratio, rather than set hematocrit values.     

Pre- vs postoperative pharmacologic inhibition of platelets: effect on intimal hyperplasia in canine autogenous vein grafts.

Several clinical studies have shown that pharmacologic inhibition of platelets can increase the patency of vascular grafts, but only if platelet-inhibition is initiated before surgery. This study was performed to compare the efficacy of pre- vs postoperative platelet-inhibition on the development of intimal hyperplasia in canine autogenous vein grafts. Reversed femoral veins were used to bypass the ligated femoral arteries in 15 dogs. End-to-side anastomoses were constructed. Eleven dogs were treated with aspirin (325 mg QD) and dipyridamole (25 mg BID). In six dogs treatment was begun 48 hours preoperatively and continued for 3 months. In five other dogs treatment was begun 48 hours after surgery and was continued for 3 months. In 4 control dogs no antiplatelet treatment was given. Excision of the vein grafts 3 months after surgery disclosed reduced intimal hyperplasia (p < 0.05) in the grafts excised from all of the treated animals as compared with those obtained from the control animals. However, there was no difference in intimal hyperplasia observed in the dogs treated both pre- and postoperatively (11 grafts) as compared with those treated only postoperatively (9 grafts). These data demonstrate that it is not necessary to begin antiplatelet therapy preoperatively in order to inhibit intimal hyperplasia. They also suggest that preoperative antiplatelet therapy may improve early graft patency by directly preventing thrombosis, not by inhibiting the development of intimal hyperplasia.     

Enhancement of antipsychotic-like effects by combined treatment with the α1-adrenoceptor antagonist prazosin and the dopamine D2 receptor antagonist raclopride in rats

Summary. Blockade of central α₁-adrenoceptors has been implicated as a possible factor contributing to the atypical antipsychotic profile of clozapine. Thus, in the present study we examined the effects of concomitant α₁-adrenoceptor and dopamine D₂ receptor blockade on conditioned avoidance response performance, as an index of antipsychotic-like activity, and on the induction of catalepsy, as a test for extrapyramidal side effect liability, in rats. It was found that pretreatment with the α₁-adrenoceptor antagonist prazosin (0.2 mg kg⁻¹ s.c.) caused an enhancement of a suppression of conditioned avoidance response in the presence of the dopamine D₂ receptor antagonist raclopride (0.05–0.20 mg kg⁻¹ s.c.). The effect was most prominent at a subthreshold dose of raclopride (0.05 mg kg⁻¹). At these doses, prazosin or raclopride by themselves, or in combination, did not produce catalepsy. In addition, pretreatment with prazosin (0.2 mg kg⁻¹ s.c.) did not alter the catalepsy produced by a higher dose of raclopride (1.0 mg kg⁻¹ s.c.). It is suggested that, in the presence of low dopamine D₂ receptor occupancy, additional α₁-adrenoceptor blockade might improve antipsychotic efficacy, and thereby improve the therapeutic window with regard to parkinsonism. Received May 19, 2000; accepted July 3, 2000     

Mice over-expressing galanin have elevated heat nociceptive threshold

The neuropeptide galanin may have a role in modulation of nociceptive input at spinal level. Here we report that mice over-expressing galanin exhibit significant elevation of nociceptive threshold to thermal stimulation in comparison to wild-type mice as assessed by the tail flick and paw heat irradiation tests. No change in response to mechanical or cold stimulation was seen. The elevated heat nociceptive threshold in the galanin over-expressing mice was reversed by intrathecal application of the putative galanin receptor antagonist M-35, galanin-(1-12)-pro-bradykinin-(2-9). The results thus support that galanin has an inhibitory function in rodent spinal cord.     

A longitudinal comparison of hypertensives and normotensives on the Wechsler Adult Intelligence Scale: initial findings

This study was designed to compare changes in performance on the Wechsler Adult Intelligence Scale over a 5- to 6-year test interval for normotensives and medically treated, uncomplicated essential hypertensives. The results indicated that normotensives improved from Time 1 to Time 2 on the Verbal scale but not on the Performance scale. Hypertensives exhibited no significant improvement or decline on either scale, although they performed less well on the Verbal scale at Time 2 than did normotensives. They also performed more poorly on the Performance scale when Time 1 and Time 2 scores were averaged. Participants who returned for Time 2 testing and those who participated only at Time 1 were compared. Verbal scaled scores at Time 1 were higher for returning than for nonreturning hypertensives, but, for normotensives, no differences were observed for those who returned for Time 2 testing and those who did not.     

A Prospective Audit of Endoscopic Vein Harvesting for Coronary Artery Bypass Surgery

INTRODUCTION

The objectives of this study were to: (i) assess the feasibility of minimally invasive endoscopic harvesting of the long saphenous vein or radial artery for use as conduit during coronary artery bypass surgery in the NHS setting; and (ii) investigate the results of endoscopic vein harvesting with regards to postoperative complications, ability to mobilise, and patient satisfaction.

PATIENTS AND METHODS

In this prospective audit, 25 consecutive patients, aged 52–90 years, undergoing either coronary artery bypass grafting alone or together with valve surgery or atrial fibrillation ablation were studied. All data were entered in purpose-designed proforma. Pre-operative risk factors including increasing age, diabetes, peripheral vascular disease, obesity, renal impairment, tobacco consumption and steroid use were documented. Time taken for harvest and conversion to traditional open vein harvest, quality of harvested vein in terms of number of repairs and vein damage were recorded. Postoperatively, we recorded harvest site wound complications, number of days to mobilise and total hospital stay. Pain score and patient satisfaction were also assessed.

RESULTS

There was one death due to myocardial infarction; another patient had postoperative cerebrovascular accident. A total of 43 lengths of grafts were harvested, 41 were long saphenous vein and two radial artery. Vein harvest time reduced significantly from a maximum of 94 min to 34 min for two lengths of long saphenous vein. Three patients required conversion from endoscopic vein harvesting to open vein harvest. The only postoperative complication directly related to endoscopic harvesting was bruising along the tunnel created by the passage of the instruments. None of the patients had any wound complication; none required antibiotics or wound debridement. Mean time to mobilise was 3.4 days. All patients who underwent successful endoscopic vein harvesting expressed satisfaction with regards to postoperative pain and cosmetic result.

CONCLUSIONS

Competence and ability to harvest conduit in an acceptable time frame are obtainable after a relatively low number of cases. The procedure is associated with a low number of postoperative complications and very high patient satisfaction.