Postoperative atrial tachyarrhythmias in patients undergoing coronary artery bypass graft surgery without cardiopulmonary bypass: a role for intraoperative magnesium supplementation.

OBJECTIVE: To determine if intraoperative magnesium supplementation would be associated with a reduction in postoperative atrial tachyarrhythmias (POAT) in patients undergoing coronary artery bypass grafting (CABG) surgery without cardiopulmonary bypass (off-pump CABG surgery). DESIGN: Retrospective study. SETTING: University Medical Center. PARTICIPANTS: Patients who had undergone off-pump CABG surgery (n = 124). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The charts of 124 patients who had undergone off-pump CABG surgery (64 by anterior thoracotomy and 60 by median sternotomy) were retrospectively reviewed. Demographic data and perioperative care were recorded and compared among patients who did and did not experience POAT and among patients who did and did not receive intraoperative magnesium supplementation. Logistic regression analysis was used to assess the association between magnesium supplementation and incidence of POAT, controlling for other covariables. Of the 124 patients, 16 had a prior history of atrial or ventricular arrhythmias and/or were receiving antiarrhythmic medications. Medical records of the remaining 108 patients were reviewed. Twenty-four patients (22%) had POAT. Forty-two patients (39%) received intraoperative magnesium. In patients receiving intraoperative magnesium, the incidence of POAT was significantly decreased (12% v 29%; p = 0.03). In these patients, initial postoperative serum magnesium was significantly higher (2.37 mEq/L v 1.86 mEq/L; p < 0.01). In patients not receiving intraoperative magnesium, 35% had hypomagnesemia (serum magnesium < 1.8 mEq/L) compared with 9% of patients receiving magnesium (p < 0.01). Patients who received intraoperative magnesium and beta-adrenergic blockers had a lower incidence of POAT (5%) than patients who received only one (19%) or neither (33%) (p < 0.05). CONCLUSIONS: Intraoperative magnesium supplementation is associated with a decrease in POAT after off-pump CABG surgery. The combination of a beta-blocker and magnesium may reduce POAT further. It is recommended that intraoperative magnesium supplementation be part of the care of patients undergoing off-pump CABG surgery.

Kainic acid lesions in adult rats as a model of schizophrenia: changes in auditory information processing.

Previous studies have suggested that intracerebroventricular kainic acid injections alter brain anatomy and neurochemistry in a manner similar to what is observed in schizophrenic patients. Disturbances in sensory information processing are one of the major symptoms of schizophrenia. Thus, the present experiments were designed to evaluate the hypothesis that hippocampal damage, induced by administration of kainic acid, would alter the processing of auditory stimuli in a paired-click paradigm. Adult male Sprague-Dawley rats were implanted for surface recording of auditory evoked potentials. At the time of electrode implantation, the rats also received bilateral injections of either kainic acid or the vehicle solution. In vehicle-treated rats, the midlatency N40 component of the auditory evoked potential was diminished in amplitude by approximately 60% in response to the second of a pair of clicks delivered 0.5 s apart. By contrast, no reduction of the N40 wave evoked by the second click was observed in kainate-treated rats. Further, administration of haloperidol, a prototypical neuroleptic agent, did not improve this auditory processing dysfunction in kainate-treated animals. Loss of auditory filtering in the paired-click paradigm and a lack of response to haloperidol in this test are typically observed in schizophrenic humans. Thus, the present results demonstrate that kainate-lesioned rats possess a functional schizophrenia-like abnormality, further reinforcing the utility of this model system for studying the basic neurobiology of schizophrenia-induced sensory processing deficits.

Rats reared in social isolation show schizophrenia-like changes in auditory gating.

Central sensory filtering processes can be demonstrated using a paired stimulus paradigm. Normal humans show a diminished vertex-recorded midlatency auditory-evoked potential to the second of paired clicks (0.5 s apart), a phenomenon termed auditory gating. Schizophrenics routinely fail to suppress the response to the second stimulus; thus, they do not gate. Previous animal studies of auditory gating have used psychotomimetic drug administration to induce a schizophrenia-like loss. However, a nonpharmacologic model of deficient gating would be advantageous. Isolation rearing of weanling rats produces impaired prepulse startle inhibition similar to that observed in schizophrenics. The present studied examined the effects of rearing status upon auditory gating. Male Sprague-Dawley rats raised in social isolation (ISO) were compared to socially raised rats (SOC). Across 10 baseline recording sessions, SOC rats showed substantial gating, while ISO rats failed to gate. Abnormal auditory gating is transiently normalized by nicotine, but not haloperidol, in schizophrenics. ISO rats given nicotine bitartrate showed gating in the normal range for 60 min. By contrast, haloperidol failed to normalize gating in ISO rats. Thus, isolation rearing of weanling rats appears to produce a stable schizophrenia-like gating deficiency that shows the same pattern of response to pharmacological interventions.

Interaction of cardiotonic thiadiazinone derivatives with cardiac troponin C.

The cardiotonic effects of thiadiazinone derivative EMD 57033 are mediated by direct actions on myofilaments (Lues, I., Beier, N., Jonas, R., Klockow, M., and Haeusler, G. J. (1993) Cardiovasc. Pharmacol. 21, 883-892). Cardiac troponin C has been postulated to be a potential target of the drug (White, J., Lee, J. A., Shah, N., and Orchard, C. H. (1993) Circ. Res. 73, 61-70). This study tested whether EMD 57033 interacts directly with recombinant human cardiac TnC (hcTnC). EMD 57033 caused concentration-dependent quenching of tyrosine (Tyr) fluorescence of hcTnC in the presence of Ca2+ (100 microM) and little change of the fluorescence in the presence of Mg2+ (2 mM). Kd for the drug-hcTnC interaction in the presence of Ca2+, determined by Tyr fluorescence titrations, was approximately 40 microM. The binding of EMD 57033 was stereo-selective: the optical isomer of EMD 57033 bound hcTnC much more weakly. The Ca2+ dependence and stereo-selectivity of EMD 57033 binding were substantiated by a dialysis-based direct binding assay. EMD 57033 was found to interfere with Ca(2+)-dependent binding of hydrophobic probe 1,1'-bi-(4-anili-no)naphthalene-5,5'-disulfonate (bis-ANS) to hcTnC. The relationships between [Ca2+] and Tyr fluorescence of hcTnC and between [Ca2+] and bis-ANS fluorescence in the presence of hcTnC were substantially altered by EMD 57033 in the range of [Ca2+] where Ca2+/Mg2+ sites of hcTnC were titrated by Ca2+. EMD 57033 was found to bind as tightly to 2 Ca2+.hcTnC as to 3 Ca(2+).hcTnC. These observations were interpreted as indicating that a EMD 57033-binding site is induced by Ca2+ binding, but not Mg2+ binding, to the Ca2+/Mg2+ sites of hcTnC. The drug-binding site most likely resides in the carboxyl domain of hcTnC.

Relaxation responses of the coronary microcirculation after cardiopulmonary bypass and ischemic arrest with cardioplegia: implications for the treatment of postoperative coronary spasm.

Coronary arteriolar spasm may occur following cardiopulmonary bypass and ischemic arrest, resulting in impaired cardiac function. Because myocardial perfusion is principally regulated by the microcirculation, the in vitro effects of various clinically used vasodilating drugs on porcine coronary microvessels less than 200 microns in diameter were examined following cardioplegic arrest and reperfusion. After 1 hour of ischemic arrest using either crystalloid or blood cardioplegia solutions followed by 1 hour of reperfusion, microvessels were studied in a pressurized (40 mmHg), no-flow state, and imaged with a video tracking device. Vessels were preconstricted by 30% to 60% of their resting diameter using acetylcholine, and various vasodilatory agents were applied extraluminally. Responses to the beta-adrenergic receptor agonist isoproterenol and the nitrovasodilator sodium nitroprusside were minimally altered by either cardioplegia solution as compared to control. In contrast, relaxation responses to both the calcium channel antagonist nifedipine and nitroglycerin were diminished after ischemic arrest and reperfusion. Relaxation responses were similar with crystalloid or blood cardioplegia for all drugs tested. Despite its somewhat attenuated response, nifedipine remained the most potent vasodilator of those studied. It is concluded that (1) following ischemic arrest with either crystalloid or blood cardioplegia solutions, responses to sodium nitroprusside and isoproterenol were minimally altered, while responses to nifedipine and nitroglycerin were attenuated; (2) relaxation responses of coronary arterioles were not significantly different with either blood or crystalloid cardioplegia; and (3) despite a slightly decreased response after cardioplegia, nifedipine was the most potent vasodilator of coronary arterioles, and may be the best choice for treating postoperative coronary arteriolar spasm.

Comparison of two transfusion strategies after elective operations for myocardial revascularization.

We performed a prospective, randomized trial of two different strategies for postoperative packed red blood cell replacement in 39 autologous blood donors undergoing elective myocardial revascularization. The "liberal" group received blood to achieve a hematocrit value of 32%, and the "conservative" group received transfusions for a hematocrit value less than 25%. Although the groups had significantly different mean hematocrit values from the fourth postoperative hour (28.7% versus 31.2%) through the fifth postoperative day (28.4% versus 31.3%), there were no significant differences in fluid requirement, hemodynamic parameters, or hospital complications. Significantly fewer units of packed cells were required in the conservatively transfused group (20 units/20 patients) compared with the liberally transfused group (37 units/18 patients) (p = 0.012). Exercise tests were performed on the fifth and sixth postoperative days, with a transfusion being given to the conservative group between tests. Although a significant improvement in exercise endurance occurred in the conservative group receiving a transfusion (p = 0.008), no significant difference in duration or degree of exercise was demonstrated between the two groups on either day. In comparing these two groups of profoundly anemic patients, we identified no adverse consequence associated with the greater degree of hemodilution and could identify no correlation between hematocrit value and exercise capacity. We conclude that although the limits of hemodilution are still poorly defined, postoperative blood transfusion in revascularized patients should be guided by clinical indications and not by specific hematocrit values.

The role of desmopressin in reducing blood loss during lumbar fusions.

The effectiveness of desmopressin (1-desamino-8-D-arginine vasopressin) in reducing intraoperative blood loss during lumbar fusions was investigated in 42 patients (52 operations) and compared with a control group of 55 patients (63 operations). The mean hemoglobin and hematocrit levels on admission and discharge were identical for both groups. Patients receiving desmopressin required less than one-half the number of autologous transfusions than the control group. Desmopressin was effective in reducing blood loss in operations in which intraoperative bleeding was greater than 1,000 milliliters, but it is probably not necessary for anticipated losses less than this amount. It may have a role in operations performed on short notice when autologous blood is usually unavailable.

Fusions and transfusions. An analysis of blood loss and autologous replacement during lumbar fusions.

Blood losses and transfusions have been analyzed prospectively for 63 lumbar fusion operations in 55 patients. The mean intraoperative loss was 550 ml, with a further 336 ml in postoperative drains. Factors increasing intraoperative loss included posterior vs. anterior approach, the use of instrumentation, multiple levels fused, male vs. female, and younger age. For anterior procedures (without instrumentation and using homograft bone) and single-level posterolateral fusions (PLF) without instrumentation, neither predeposit nor intraoperative salvage (cell saver) was required. Single-level PLF with instrumentation and two-level PLF without instrumentation required either cell saver or predeposit of one or two units. Multiple-level PLF with instrumentation and all 360 degrees procedures required cell saver and two units of predeposit. Two patients received homologous blood.

The efficacy of postoperative autotransfusion in patients undergoing cardiac operations.

The efficacy of postoperative autotransfusion in lowering the requirement for banked-blood transfusion was studied in two groups, each having 168 patients, who underwent cardiac operations between April, 1979, and May, 1980. A Sorenson autotransfusion system was available for use in the autotransfusion group, whereas the control group received routine closed mediastinal drainage. Of the autotransfusion group, 81% met the criterion for autotransfusion (mediastinal losses of 450 ml or more during 4 hours), but only 61% of the autotransfusion group actually received autologous blood (mean autotransfusion volume, 399 +/- 25 ml). The patients receiving autologous blood required significantly less banked blood than their matched controls (447 +/- 60 ml and 744 +/- 83 ml, respectively; p less than 0.001). In the subgroup of patients with large mediastinal losses (more than 1,250 ml), this difference was even greater (autotransfusion, 642 ml compared with control, 1,145 ml; p less than 0.01). Postoperative autotransfusion is a simple, safe, and cost-effective method to reduce dependence on banked blood, especially when mediastinal losses are large. Obtaining maximum benefit requires familiarity of staff with the system and use of a consistent protocol.