Strokes after cardiac surgery: mostly right hemispheric ischemic with mild residual damage.

OBJECTIVE: Since cardiac surgery is now performed on patients with high risk for cerebrovascular disease, we studied the clinical findings and medium term outcome of patients with acute stroke/transient ischemic attack (TIA) after cardiac surgery. METHODS: All consecutive patients with acute stroke/TIA after cardiac surgery were prospectively observed during a 19 month period. Follow-up was between 3 months and 21 months. Risk factors, type of stroke, anatomic localization, initial neurological deficit and followup outcome were evaluated, using standard assessment scores. RESULTS: Among 406 patients operated (mean age 64.3 +/- 12.7 years, 284 males), 18 developed stroke and 2 TIAs (mean age 65.7 years, 13 males). There were no cases of intracerebral hemorrhage. Most of the strokes happened shortly after valve surgery (mean 1.3 days post operatively) and were right hemispheric (right = 11, left = 3; p = 0.034). Vertebrobasilar stroke appearance was delayed (mean: 8.25 days post operatively); they were attributed mostly to cardiac arrhythmias. Stroke/TIA patients did not have a higher preoperative risk than those without, but their cardiac functional score was worse (p = 0.01), and the average cardiopulmonary bypass time during surgery was longer (p = 0.009). Two patients died in hospital, both with vertebrobasilar stroke. Most of the hemispheric stroke patients became functionally independent (mean modified Rankin Scale < 2), even those with initial severe deficit. CONCLUSION: Strokes after cardiac surgery are mostly right hemispheric and exclusively ischemic. Outcome is relatively fair. We suggest an embolic injury to the right hemisphere, procedure related, as a possible mechanism.

Mitral valve repair in severe ischemic cardiomyopathy.

BACKGROUND: Patients with ischemic mitral valve insufficiency (MR) and poor left ventricular (LV) function present a high operative risk. Whether to repair or replace these valves is controversial, while some suggest that heart transplant offers a better solution. We investigated our early and late results in this difficult subset of patients. METHODS: Between 1993-1999,115 patients underwent mitral valve repair (MVR) in our department. Twenty-one patients had severe LV dysfunction with ejection fraction < 25%. Mean age was 60 years (range 45-81). Nineteen (90%) were in New York Heart Association (NYHA) Class IV, 7 (33%) underwent emergency surgery, 3 (14%) were in cardiogenic shock, and 2 (10%) were taken to the operating room under cardiopulmonary resuscitation. All underwent coronary artery bypass grafting (CABG) in addition to MVR, with a mean number of grafts 2.9 per patient. RESULTS: There were no early operative deaths. The average stay in intensive care was 5.9 days (range 1-52). There were three late deaths (14%). Follow-up evaluation up to 3 years showed marked improvement in clinical status. Twelve (67%) patients are in NYHA Class I-II, and three (17%) in Class III. Echocardiography revealed good function of the mitral valve in all, although overall LV function did not change significantly. CONCLUSION: (1) MVR in patients with severe ischemic cardiomyopathy can be accomplished with excellent results. (2) There is marked symptomatic improvement in these patients, even though LV function did not seem to be improved. (3) Long-term survival still needs to be defined.

Exercise hemodynamics of aortic prostheses: comparison between stentless bioprostheses and mechanical valves.

BACKGROUND: Nonstented bioprostheses have been associated with lower resting gradients than stented bioprostheses or mechanical valves. We compared the hemodynamic performance of nonstented bioprostheses and mechanical valves with normal native aortic valves at rest and exercise. METHODS: Dobutamine echocardiography was used to assess gradients and effective orifice area index at rest and exercise in patients with the Toronto stentless porcine valve (TSPV; n = 13; mean implant size 25.7 mm), Medtronic Freestyle (FR; n = 11; mean implant size 23.9 mm), Sorin Bicarbon (SOR; n = 11; mean implant size 24.5 mm), St. Jude Medical (SJM; n = 10; mean implant size 21.3 mm), and normal native aortic valves (NOR; n = 10). RESULTS: All groups demonstrated a major rise in cardiac output at maximal dobutamine infusion. At rest and exercise, respectively, mean gradients were 5.48 +/- 1.1 mm Hg and 5.83 +/- 0.9 mm Hg for TSPV, 5.68 +/- 1.2 mm Hg and 7.50 +/- 1.7 mm Hg for FR, 10.29 +/- 1.4 mm Hg and 20.78 +/- 2.7 mm Hg for SJM, 5.26 +/- 0.8 mm Hg and 11.1 +/- 1.8 mm Hg for SOR, and 1.54 +/- 0.4 mm Hg and 2.18 +/- 0.7 mm Hg for NOR. In comparison with normal valves, both stentless groups showed no change in mean gradient at exercise, whereas both mechanical groups showed an increase in gradient at exercise (p < 0.04). CONCLUSIONS: Stentless valves behave similarly to normal aortic valves in that there is almost no increase in gradient at exercise. Both mechanical valve groups showed increased gradients at exercise, suggesting that these valves obstruct blood flow. Our data add further evidence that stentless valves are hemodynamically superior to mechanical valves in the aortic position.

Memory-enhancing effects of DHEAS in aged mice on a win-shift water escape task.

The steroid hormone, dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) have been implicated in age-associated deficits in memory. Numerous studies have demonstrated the effectiveness of these neurosteroids to enhance retention and ameliorate the effects of various memory-blocking agents, but few studies have directly assayed their effects on memory in aged animals. The present study investigated the memory-enhancing effects of DHEAS in a win-shift (nonmatching-to-sample) task in aged mice using water escape motivation. Sixteen CD-1 mice, 18-20 months old, were trained to a moderate criterion of 7/10 correct trials and were then divided into two equal groups based on acquisition performance. One group received oral administration of DHEAS (1.5 mg/mouse/day) in a vehicle solution (0.0015% methyl salicylate) while the other group received the vehicle alone. DHEAS effects were assessed using a procedure in which delay intervals (0, 120, and 240 s) were interposed between sample and comparison trials over the course of three test sessions. The group receiving DHEAS recorded significantly higher retention scores across 3 days of testing, particularly at the 120-s delay interval, indicating that DHEAS enhanced working memory in these aged animals.

[Surgical repair of myxomatous mitral valve].

Myxomatous mitral valve disease is now the most common cause of mitral regurgitation in the western world. Repair of the leaking valve has become standard surgical procedure during the past 2 decades. Between 1993-1999 we performed 113 repairs of the mitral valve. In 25 patients the etiology was myxomatous degeneration (no mortality). Long-term clinical results depend on patients' functional class at surgery. Based on this fact, and the good surgical results, it is recommended to refer such patients even with severe mitral incompetence for surgery at an early stage, even if symptoms are minimal.

Effect of surgical repair of secundum-type atrial septal defect on right atrial, right ventricular, and left ventricular volumes in adults.

Surgical repair of atrial septal defect in adults reduces right ventricular and right atrial diameters and volumes, and improves left ventricular filling.

The neurosteroid pregnanolone prevents the anxiogenic-like effect of inescapable shock in the rat.

RATIONALE AND OBJECTIVES: The ability of progesterone (P4) and its neurosteroid metabolite, 3alpha-OH-5beta-pregnan-20-one (pregnanolone) in protecting against the anxiogenic-like effect of inescapable shock (IS) in male rats was examined, as these steroids exert anxiolytic, anticonvulsant, and ataxic effects similar to the benzodiazepines (BZ), drugs shown to prevent IS-induced anxiogenesis. METHODS: Adult male rats were injected with pregnanolone (8 mg/kg, SC), P4 (4 mg/rat) or its appropriate vehicle before exposure to IS. Twenty-four hours later, animals were injected with the steroid or its vehicle and then tested in the elevated plus-maze. In a control experiment, animals were injected with chlordiazepoxide (CDP, 15 mg/kg, IP) or vehicle before IS, and tested in the plus-maze 24 h later. RESULTS: Whereas CDP or pregnanolone before IS resulted in the loss of the anxiogenic-like response seen 24 h after IS, P4 before IS did not protect against the anxiogenic-like effect of IS. The acute anxiolytic-like effect of pregnanolone and P4 was lost in animals that were injected with vehicle before the IS, but was observed in animals that were injected with the steroids before IS. Moreover, P4 injection in non-shocked animals was associated with an anxiogenic-like response observed 24 h after steroid administration. CONCLUSION: The protection against the effect of IS afforded by a GABAergic neurosteroid is comparable to that observed with BZs, and thus provides further evidence of an allosteric relationship between the neurosteroid and BZ binding site on the GABA(A) receptor complex.

Activation of peripheral mitochondrial benzodiazepine receptors in the hippocampus stimulates allopregnanolone synthesis and produces anxiolytic-like effects in the rat.

RATIONALE AND OBJECTIVES: Stimulation of the mitochondrial benzodiazepine receptor (MBR) in the brain activates the synthesis of neurosteroids that can act as positive modulators of the GABA(A) receptor complex. Allopregnanolone is a potent anxiolytic, anticonvulsant, sedative and hypnotic GABAergic neurosteroid. The anxiolytic-like effects of FGIN 1-27, an MBR agonist, were determined after microinjection into the dorsal hippocampus. METHODS: Behavior in the elevated plus-maze was assessed in adult male rats after bilateral injections of 0, 1.25, 2.5, or 5 microg FGIN 1-27. The behavioral effects of FGIN 1-27 were also determined in animals receiving intrahippocampal co-administration of 20 ng picrotoxin, 5 microg flumazenil, or 200 ng PK 11195. The effects of FGIN 1-27 on behavior in the elevated plus-maze and shock-probe burying test were measured in animals pretreated systemically with 10 mg/kg 4-MA, a 5alpha-reductase inhibitor. Hippocampal and blood plasma levels of allopregnanolone were measured in separate groups of animals pretreated with 4-MA and receiving an intrahippocampal injection of FGIN 1-27. RESULTS: Intrahippocampal injections of FGIN 1-27 produced anxiolytic-like effects in the plus-maze and in the shock-probe burying test. Hippocampal and blood levels of allopregnanolone were also increased by FGIN 1-27. The anxiolytic-like effects of FGIN 1-27 were attenuated by PK 11195 and were blocked by picrotoxin and 4-MA pretreatment, but remained unaffected by flumazenil pretreatment. The neurosteroidogenic effect of FGIN 1-27 was also eliminated by 4-MA. CONCLUSION: Activation of the MBR in the hippocampus leads to the synthesis of allopregnanolone, an anxiolytic neurosteroid that potentiates GABA(A) receptor function.

[Mitral valve repair in ischemic cardiomyopathy with severe left ventricular dysfunction].

Patients with ischemic mitral insufficiency and poor left ventricular function are high operative risks. We present 101 patients who had mitral valve repair in our department: 21 had severely reduced left ventricular function, 19 were in NYHA functional Class IV, and 2 in Class III. All had concomitant coronary artery bypass. There was no early operative mortality, but there were 2 late deaths (9.6%). At follow-up (3-36 months) all valves were functioning normally, 9 patients (43%) were in NYHA functional Class I, and 4 (19%) in Class II. Our experience shows that repair of ischemic mitral insufficiency in the presence of severe left ventricular dysfunction can be performed with good results, and is preferable to mitral valve replacement. Late follow-up showed significant symptomatic improvement.

Transradial catheterization: a word of caution.

The radial artery has been used as an access for transcatheter procedures as well as a source for arterial conduit during coronary bypass surgery. It has been reported that 5Eth 13% of radial arteries may be damaged during transradial catheterization. The damage can be irreversible, and may therefore prohibit the radial arteryOs subsequent utilization as a coronary conduit.

Anxiolytic effects of the neuroactive steroid pregnanolone (3 alpha-OH-5 beta-pregnan-20-one) after microinjection in the dorsal hippocampus and lateral septum.

The anxiolytic effects of the neuroactive steroid, 3 alpha-OH-5 beta-pregnan-20-one (pregnanolone), were determined after injection into the dorsal hippocampus or lateral septum in adult male rats. An increase in the proportion of time spent on the open arms of the elevated plus-maze was found after 2.5 and 5 micrograms of pregnanolone in the hippocampus, but not in the lateral septum. Intrahippocampal injection of 2.5 micrograms of the 3 beta-epimer of pregnanolone did not affect behavior in the plus-maze; a higher dose of 5 micrograms produced an anxiogenic effect. In the shock-probe burying test latency to burying behavior was increased by intrahippocampal or intraseptal injection of 2.5 and 5 micrograms of pregnanolone; the duration of burying behavior was decreased by 0.5, 2.5 and 5 micrograms of pregnanolone injection in the dorsal hippocampus or lateral septum. The number of contacts with the shock probe was not affected by any dose of pregnanolone in either intracranial site of injection. The anxiolytic effects of intrahippocampal or intraseptal injection of pregnanolone were blocked by intracranial pretreatment with 20 ng of picrotoxin, but not by microinjection of 5 micrograms of flumazenil or 200 ng of PK 11195. Thus, inhibition of the hippocampus, mediated by the pregnanolone's action at the GABAA receptor, produces a general anxiolytic effect. However, similar inhibition in the lateral septum attenuates active avoidance of anxiogenic stimuli (i.e., decreased burying behavior), but not passive avoidance of aversive stimuli (i.e., exploration of open arms of the plus-maze and number of shocks in the probe burying test).

Ovarian steroids and stress produce changes in peripheral benzodiazepine receptor density.

Although past research has described changes in the density of the peripheral benzodiazepine receptor in brain and in peripheral organs in response to stressors and steroid hormone exposure, their combined influence had yet to be determined. This study examined the effect of swim-stress as a function of ovarian hormone administration on the binding of an isoquinoline carboxamide derivative, [3H]PK 11195, in brain and peripheral tissues. In olfactory bulb and adrenal gland, stress increased peripheral benzodiazepine receptor density in ovariectomized rats with and without estradiol and progesterone replacement injection, even when compared with unstressed animals treated with hormones, where estradiol + progesterone decreased peripheral benzodiazepine receptor number in olfactory bulb, but estradiol and estradiol + progesterone increased it in adrenal gland. In frontal cortex, stress decreased peripheral benzodiazepine receptor number, an effect that was reversed by estradiol. In hippocampus estradiol decreased peripheral benzodiazepine receptor density in unstressed animals and estradiol + progesterone decreased peripheral benzodiazepine receptor number in unstressed and stressed animals. In cerebellum, stress, estradiol and estradiol + progesterone alone decreased peripheral benzodiazepine receptor density. In uterus of unstressed controls, estradiol + progesterone increased peripheral benzodiazepine receptor density, and stress produced a further increase in steroid-treated females. Stress did not affect peripheral benzodiazepine receptor density in kidney, except in animals that received estradiol + progesterone injections, where swim-stress produced a significant decrease in peripheral benzodiazepine receptor density. Thus, steroid hormones regulate peripheral benzodiazepine receptor density in endocrine organs and brain, and the hormonal state of the organism modifies the peripheral benzodiazepine receptor response to stress in a tissue- and brain region-specific manner, suggesting that the peripheral benzodiazepine receptor may play a pivotal role in an integrated response to stress.

Corticosterone is permissive to the anxiolytic effect that results from the blockade of hippocampal mineralocorticoid receptors.

The effects of RU 28318, a mineralocorticoid receptor antagonist (A-MR), and RU 38486, a glucocorticoid receptor antagonist (A-GR) on behavior in three animal models of anxiety were assessed after microinjection into the dorsal hippocampus. Significant anxiolytic effects were observed after intrahippocampal injection of 0.5, and 1 ng of A-MR in thigmotaxic behavior in the open field, in the elevated plus-maze, and in the defensive burying test. Lower (0.2 ng) or higher (5 ng) doses of A-MR were ineffective, as were comparable injections of A-GR or microinjections of combined A-MR and A-GR. The anxiolytic effect of intrahippocampal A-MR administration observed in the elevated plus-maze and in the open field was not observed in adrenalectomized animals or in animals pretreated with a systemic injection of dexamethasone (80 mg/kg). Intrahippocampal injection of 1 ng of A-MR or A-GR prevented the return to basal corticosterone levels observed 90 min after restraint stress. This effect was reversed in dexamethasone-pretreated animals. The results are discussed in light of recent findings implicating the role of the MR in the hippocampus in adaptive behavioral responses to an aversive or threatening environment, and further implicate the permissive role of corticosterone in A-MR-induced behavioral responses.

Withdrawal from 3alpha-OH-5alpha-pregnan-20-One using a pseudopregnancy model alters the kinetics of hippocampal GABAA-gated current and increases the GABAA receptor alpha4 subunit in association with increased anxiety.

In the present study, we have characterized properties of steroid withdrawal using a pseudopregnant rat model. This paradigm results in increased production of endogenous progesterone from ovarian sources and as such is a useful physiological model. "Withdrawal" from progesterone induced by ovariectomy on day 12 of pseudopregnancy resulted in increased anxiety, as determined by a decrease in open arm entries on the elevated plus maze compared to control rats and pseudopregnant animals not undergoing withdrawal. Similar findings were obtained 24 hr after administration of a 5alpha-reductase blocker to a pseudopregnant animal, suggesting that it is the GABAA-modulatory 3alpha-OH-5alpha-pregnan-20-one (3alpha, 5alpha-THP) that produces anxiogenic withdrawal symptoms. Twenty-four hours after steroid withdrawal, the time constant for decay of GABAA-gated current was also reduced sixfold, assessed using whole- cell patch-clamp procedures on pyramidal neurons acutely dissociated from CA1 hippocampus. Thus, 3alpha,5alpha-THP withdrawal results in a marked decrease in total GABAA current, a possible mechanism for its anxiogenic, proconvulsant sequelae. In addition, 3alpha,5alpha-THP withdrawal resulted in insensitivity to the normally potentiating effect of the benzodiazepine lorazepam (LZM) on GABAA-gated Cl- current. This withdrawal profile is similar to that reported for other GABAA-modulatory drugs such as the benzodiazepines (BDZs), barbiturates, and ethanol. These changes were also associated with significant two and threefold increases in both the mRNA and protein for the alpha4 subunit of the GABAA receptor, respectively, in hippocampus. The pseudopregnancy paradigm may be a useful model for periods of endogenous 3alpha,5alpha-THP withdrawal such as premenstrual syndrome and postpartum or postmenopausal dysphoria, when increased emotional lability and BDZ insensitivity have been reported.

The Sorin Bicarbon valve: clinical evaluation in Israel.

BACKGROUND: Four collaborating centers pooled their results with the Sorin Bicarbon Bileaflet valve. MATERIAL AND METHODS: Between 6/91 and 11/95, 431 patients, 235 males and 196 females, underwent valve replacement using the new Sorin prosthesis; age range: 16-88, mean 61.4 yrs. OPERATIONS: AVR - 206, MVR - 177, TVR - 1, DVR - 47. Additional procedures - 139: CAB -117, valve repair - 22. AV sizes: 19-27, MV sizes: 21-33. RESULTS: Thirty day mortality was 4.3%. Early complications included: CVA - 1.4%, +ve blood culture - 2%, reop for bleeding - 5%. Late complications: infective endocarditis - 2.3%, valve thrombosis - 0.2%, thromboemboli - 2.5%, major bleeding - 1.6%, reoperation - 3%, late deaths (all causes) - 4.3%. No structural deterioration has been reported with this valve and acceptable gradients have been observed. Hemolysis is negligible. CONCLUSIONS: Based on this intermediate experience the Sorin Bicarbon prosthesis is well-designed with good hemodynamic properties, and an acceptably low incidence of complications.

Femoro-femoral bypass for repeat open-heart surgery.

Repeat open-heart operations are becoming more frequent with a patient population at higher risk. Sternal re-entry poses the risk of possible damage to vital structures. These include laceration of the myocardium, especially the right ventricle, tearing of patent grafts and internal mammary grafts in particular, or dislodgement of emboli from patent vein grafts. To minimize the risk associated with sternal re-entry, we adopted the method of establishing femoral artery-femoral vein cardiopulmonary bypass (CPB) in order to achieve cardiac decompression prior to sternotomy. Between June 1994 and October 1997, 94 patients underwent repeat open-heart operations at our institution. Of these, seven were a second time reoperation. Mean age was 62 years (range 31-80 years), and 65 were male. Fifty-nine patients had coronary bypass, 27 had aortic valve replacement, 45 had mitral valve replacement, and nine had other procedures (these numbers include patients having combined procedures). In patients with no known vascular disease, the femoral vessels were exposed, and if found suitable, were cannulated, and the patients connected to CPB. The sternum was opened with an oscillating saw, and on penetration through the posterior table, the heart was drained to allow for decompression. If the femoral vein cannula did not allow full bypass, ventilation was maintained until the right atrium was exposed and cannulated and full bypass was achieved. Femoro-femoral bypass was established in 75 patients. In 19 patients it was not done for the following reasons: eight patients had a diseased femoral artery, in one patient the femoral vein could not be cannulated, nonuse of CPB altogether occurred in three patients, and it was because of surgeon's preference in seven patients. In one patient a high pressure developed in the arterial line, requiring conversion to aortic cannulation during the course of CPB, without any negative consequences. There were no problems associated with sternal re-entry, no patient had limb ischemia or venous thrombosis. Two patients (2.6%) had complications related with femoral cannulation, with one having trauma to an atherosclerotic femoral artery requiring repair with vein interposition, and the other a tear of iliac vein requiring laparotomy. Groin wound infection occurred in five patients (6.6%), and groin hematoma in four patients (5.3%). All complications were treated successfully with no permanent damage. Operative mortality was 9% (seven patients). Causes of death included myocardial infarction (2), infection (3), respiratory (1), and cirrhosis (1). We conclude that femoro-femoral bypass prior to sternotomy is a safe and easy method to reduce the risk of sternal re-entry by allowing early decompression of the heart, and in unstable patients it offers better myocardial protection by earlier connection to CPB. Proper selection of patients is important in order to minimize related comorbidity. We recommend this method in redo patients in whom femoral cannulation is feasible.

Comparison of exercise hemodynamics among nonstented aortic bioprostheses, mechanical valves, and normal native aortic valves.

BACKGROUND: While aortic valve prostheses are known to perform well at rest, few studies have examined them under stress. We compared stress hemodynamics of mechanical valves and nonstented porcine valves in the aortic position to that of normal native aortic valves. METHODS: Dobutamine echocardiography was used to assess mean and peak gradients and effective orifice area index (EOAI) at rest and exercise in patients with the Toronto Stentless Porcine Valve (SPV) (n = 13, mean implant size 25.7 mm), Sorin Bicarbon mechanical valve (SOR) (n = 11, mean implant size 24.5 mm), and patients with normal native aortic valves (NOR) (n = 10). Dobutamine infusion was started at 5 micron/kg per minute, and increased by increments of 5 micron/kg per minute until the target heart rate was achieved or until a maximal dose of 40 micron/kg per minute. RESULTS: At rest and exercise, respectively, cardiac output (L/min) was 5.2 and 10.4 for Toronto SPV; 7.4 and 13.5 for SOR; and 4.6 and 11.2 for NOR. Measured EOAI (cm2) was 1.1+/-0.2 and 1.15+/-0.2 for TORONTO SPV; 1.60+/-0.3 and 1.58+/-0.3 for SOR; and 1.45+/-0.2 and 1.46+/-0.2 for NOR. Mean gradients (mmHg) were 5.48+/-1.1 and 5.83+/-0.9 for TORONTO SPV; 5.26+/-0.8 and 11.3+/-1.8 for SOR; and 1.54+/-0.4 and 2.18+/-0.7 for NOR. Peak gradients (mmHg) were 11.9+/-2.0 and 21.0+/-3.7 for TORONTO SPV; 10.79+/-1.7 and 25.9+/-3.4 for SOR; and 2.38+/-0.9 and 6.1+/-2.3 for NOR. CONCLUSIONS: Although the mechanical group (SOR) had larger measured EOAI, the greater increase in gradients with exercise in this group suggests that the TORONTO SPV is less obstructive to flow.