Serum relaxin levels and kidney function in late pregnancy with or without preeclampsia.

OBJECTIVE: Relaxin, a potent pregnancy-related hormone, has been proposed to be a major mediator of renal physiology in normal pregnancy. We wished to test relaxin levels in pregnancy and preeclampsia. METHODS: We performed precise physiologic measurements of kidney function in 38 normal peripartum women and 58 women with preeclampsia. We measured serum relaxin levels prior to delivery and over the first 4 postpartum weeks utilizing a modern, validated ELISA. Results were compared to those of 18 normal women of childbearing age. RESULTS: Relaxin levels were substantially elevated in women prior to delivery (364 ± 268 vs. 15 ± 16 pg/ml) and fell rapidly over the first postpartum week reaching normal non pregnant levels by Week 2 (32 ± 64 vs. 15 ± 16 pg/ml). No differences were seen between relaxin levels in normal pregnancy as compared to preeclampsia (364 ± 268 vs. 376 ± 241 pg/ml) despite substantial and persistent abnormalities in GFR (149 ± 33 vs. 89 ± 25 ml/min), albuminuria (14 vs. 687 mg/g) and mean arterial pressure (80 ± 8 vs. 111 ± 18). Furthermore no correlation could be established between physiologic measures (GFR, MAP, RBF, RVR) and relaxin levels (p > 0.3), either in the overall population or any of the subgroups. CONCLUSION: Relaxin is indeed significantly elevated in the serum of women during late pregnancy and the early puerperium. However, serum relaxin does not appear to influence BP, renal vascular resistance, renal blood flow or GFR in late pregnancy or in women with preeclampsia.

Nature of the renal injury following total renal ischemia in man.

The effects of total renal ischemia (TRI) of 15-87 min duration due to suprarenal clamping of the aorta were studied in 15 mannitol-treated patients undergoing abdominal aortic surgery. 15 patients undergoing similar surgery but requiring only infrarenal clamping served as controls. 1-2 h following TRI, GFR was reduced to only 39% of that in controls, 23 +/- 5 vs. 59 +/- 7 ml/min (P less than 0.001). This could not be ascribed to impaired renal plasma flow (RPF), which was mildly reduced to 331 +/- 71 and was not different from the value in controls, 407 +/- 66 ml/min. However, impaired PAH extraction (43 +/- 7%) and isosthenuria, not present in controls, suggest a primary role for tubular injury in lowering GFR at this time. 24 h following TRI, the GFR remained depressed below controls, 45 +/- 8 vs. 84 +/- 8 ml/min (P less than 0.005), while the transglomerular sieving of neutral dextrans was significantly enhanced (radius interval, 24-40 A). A theoretical analysis of transcapillary solute exchange revealed that these findings could be largely explained by a selective reduction of either RPF (-61%) or of transmembrane hydraulic pressure difference (-18%) below control values. Alternately, a combination of these two factors with changes of smaller magnitude could explain the findings. In contrast, a selective increase in oncotic pressure or decrease of the glomerular ultrafiltration coefficient could be excluded as a cause of hypofiltration 24 h after TRI. These observations lead us to suggest that the transient azotemia observed following TRI is due to a self-limited injury to the nephron that is identical to that seen in overt and sustained forms of acute renal failure.

Effect of L-arginine therapy on the glomerular injury of preeclampsia: a randomized controlled trial.

OBJECTIVE: To assess the benefit of l-arginine, the precursor to nitric oxide, on blood pressure and recovery of the glomerular lesion in preeclampsia. METHODS: Forty-five women with preeclampsia were randomized to receive either l-arginine or placebo until day 10 postpartum. Primary outcome measures including mean arterial pressure, glomerular filtration rate, and proteinuria were assessed on the third and 10th days postpartum by inulin clearance and albumin-to-creatinine ratio. Nitric oxide, cyclic guanosine 3'5' monophosphate, endothelin-1, and asymmetric-dimethyl-arginine and arginine levels were assayed before delivery and on the third and 10th days postpartum. Healthy gravid women provided control values. Assuming a standard deviation of 10 mm Hg, the study was powered to detect a 10-mm Hg difference in mean arterial pressure (alpha .05, beta .20) between the study groups. RESULTS: No significant differences existed between the groups with preeclampsia before randomization. Compared with the gravid control group, women with preeclampsia exhibited significantly increased serum levels of endothelin-1, cyclic guanosine 3'5' monophosphate, and asymmetric-dimethyl-arginine before delivery. Despite a significant increase in postpartum serum arginine levels due to treatment, no differences were found in the corresponding levels of nitric oxide, endothelin-1, cyclic guanosine 3'5' monophosphate, or asymmetric-dimethyl-arginine between the two groups with preeclampsia. Further, there were no significant differences in any of the primary outcome measures with both groups demonstrating similar levels in glomerular filtration rate and equivalent improvements in both blood pressure and proteinuria. CONCLUSION: Blood pressure and kidney function improve markedly in preeclampsia by the 10th day postpartum. Supplementation with l-arginine does not hasten this recovery. LEVEL OF EVIDENCE: I.

Long-term follow-up after surgical correction of Wolff-Parkinson-White syndrome.

The long-term efficacy of surgical correction of Wolff-Parkinson-White syndrome was evaluated in 45 consecutive patients. Before surgery, 42 patients had reciprocating tachycardia and 12 had atrial fibrillation. The principal operative procedure was endocardial incision in 42 patients, endocardial cryoablation in 2 patients and epicardial cryoablation without dissection of the atrioventricular (AV) fat pad in 1 patient. Two patients had perioperative complications. One patient had bleeding that necessitated reoperation, and one had a right cerebral stroke with subsequent clearing of neurologic deficit. At postoperative electrophysiologic study, only the patient who underwent epicardial cryoablation had conduction over an accessory connection. Two others had intermittent delta waves in the early postoperative period but no accessory connection conduction at electrophysiologic study. During a mean follow-up of 3.1 years, the patient with ineffective cryoablation had recurrent orthodromic tachycardia, and one other patient had late recurrence of delta waves without arrhythmias. Four other patients had frequent palpitation, which was caused by premature ventricular complexes in three and sinus tachycardia in one. Seventeen patients had occasional "skipped beats" without recurrence of tachyarrhythmias. Twelve of 13 patients whose arrhythmias limited employment before surgery returned to work after surgery. By actuarial analysis at 1, 2 and 3 years, all patients were alive and 98% were free from tachyarrhythmias. Surgical correction of Wolff-Parkinson-White syndrome provides excellent long-term results with low morbidity. Patients who are disabled by arrhythmias return to work after successful surgery. Delta waves may persist or recur without return of arrhythmias. Minor postoperative episodes of palpitation are common and do not correlate with tachyarrhythmias.

Chronic injury of human renal microvessels with low-dose cyclosporine therapy.

Physiologic and morphologic techniques were used to study kidneys of cardiac transplant recipients treated with either low-dose (low-CsA) or high-dose (high-CsA) cyclosporine. After 12 months both low-CsA (4.6 +/- 0.4) and high-CsA (6.3 +/- 0.3 mg/Kg/24 hr, p less than 0.01) were associated with azotemia and hypertension; GFR with each regimen was depressed below values in a third group treated without CsA (no-CsA) by 40-47%, while corresponding renal vascular resistance was elevated greater than 2-fold (P less than 0.01). Morphologic changes in both CsA groups included an obliterative arteriolopathy with downstream collapse or sclerosis of glomeruli. Determination of renal arcuate vein occlusion pressure revealed an increasing renal artery-to-peritubular capillary pressure gradient between 1 and 12 months of CsA therapy. Fractional clearances of dextrans of graded size were elevated at each time compared with the no-CsA group. Analysis of dextran transport with an isoporous membrane model indicates that transglomerular hydraulic pressure difference (delta P) approximated 39 with no-CsA, but was reduced with low-CsA therapy to about 30 at 1 month, and about 34 mmHg after 12 months. We conclude that chronic CsA therapy induces constriction and eventual occlusion of afferent arterioles, causing downstream glomerular damage that is irreversible. Low versus high dosage of CsA confers only marginal protection against this serious microvascular injury.

Vulnerability of patients with obstructive hypertrophic cardiomyopathy to ventricular arrhythmia induction in the operating room. Analysis of 17 patients.

To evaluate vulnerability to ventricular arrhythmia induction, programmed electrical stimulation was performed in the operating room in 17 consecutive patients undergoing myotomy-myectomy for obstructive hypertrophic cardiomyopathy (HC). A control group of 5 patients undergoing coronary artery bypass grafting with normal left ventricular function and no previous myocardial infarction also was tested. Of the 17 patients with HC, 14 had inducible sustained ventricular tachycardia (VT) or ventricular fibrillation (VF), 1 had inducible unsustained VT and the remaining 2 had less than 6 ventricular beats. In contrast, none of the 5 control patients had an inducible sustained ventricular arrhythmia, 1 had inducible unsustained VT, and the remaining 4 had less than 3 ventricular beats. The difference between the 2 groups with respect to induction of a sustained ventricular arrhythmia, unsustained VT or less than 6 ventricular beats was significant (p less than 0.001). It is concluded that patients with severe obstructive HC are unusually vulnerable to ventricular arrhythmia induction. This suggests that spontaneous ventricular tachyarrhythmias may be an important cause of sudden death in patients with HC.

Action of drugs in patients early after cardiac surgery. I. Comparison of isoproterenol and dopamine.

Dopamine and isoproterenol were each administered in two different doses to 12 patients with coronary artery disease in the period immediately after open heart surgery. The two doses of dopamine resulted in respective increases in cardiac output of 23 and 43 percent and reductions in systemic vascular resistance of 23 and 32 percent; neither dose significantly altered heart rate. The two doses of isoproterenol caused respective increases of 23 and 37 percent in cardiac output and 18 and 28 percent in heart rate and reductions in systemic vascular resistance of 22 and 29 percent. We conclude that lack of chronotropic effect of dopamine as compared with isoproterenol may make the former the agent of choice in patients requiring inotropic agents for their care in the early period after cardiac surgery.

Sequential pathophysiological changes characterizing the progression from renal dysfunction to acute renal failure following cardiac operation.

Sequential pathophysiological data were analyzed from 14 patients who exhibited similar severe depression of cardiac and renal function within 24 hours of cardiac operation. Seven patients exhibited postoperative renal dysfunction (defined by a minimum postoperative clearance of inulin [Cin] between 20 ml/min/1.73 m2 and one-half normal) and seven progressed from renal dysfunction to acute renal failure (ARF) (Cin less than or equal to ml/min/1.73 m2). In ARF patients depression of cardiac function was profound and persistent from postoperative days 1 to 7. Urine flow remained greater than 1 ml/min, and serum creatinine rose progressively. The Cin declined progressively during the first postoperative week. The ratio or urinary to plasma osmolality fell, and the fractional excretion of sodium (FENa) and potassium (FEK) increased substantially. By contrast, in renal dysfunction patients definite hemodynamic improvement occurred and renal function remained stable. Increased FENa in renal dysfunction was associated with hemodynamic improvement, weight loss, and stable fractional potassium excretion. These data provide unique documentation of the indices of hemodynamic and renal function associated with the progression to postoperative ARF. The central role of sustained profound depression of cardiac function in this progression appears to be the primary factor in the lethality of postoperative ARF.

Relative contributions of the anterior and posterior mitral chordae tendineae to canine global left ventricular systolic function.

The relative importance of the anterior and posterior mitral chordae tendineae to global left ventricular performance, independent of load, was determined by sequentially measuring the slope of the left ventricular peak isovolumetric pressure-volume relation in a canine model with the chordae of both, either, and neither mitral leaflet(s) intact. The order in which the chordae were severed was randomly assigned. Compared to baseline values (both chordae intact), severing the chordae of the anterior leaflet (posterior leaflet chordae intact) reduced the slope of the pressure-volume relation by 27% (p = 0.005) in 10 dogs; the slope decreased by an additional 16% (p = 0.017) when the posterior chordae were subsequently severed in this group. In 10 dogs randomized to the reverse order, the slope of the pressure-volume relation decreased by 17% (p = 0.021) after the posterior chordae were severed (anterior leaflet chordae intact); an additional 24% decrease in the slope (p = 0.001) occurred when the chordae of the anterior leaflet were subsequently severed in this group. The chordae of the anterior and posterior mitral leaflets have an additive, but statistically indistinguishable (p = 0.140), influence upon global left ventricular systolic performance; however, the contribution of the anterior chordae tends to be more important. Thus preservation of the anterior mitral leaflet and its chordal attachments to the papillary muscles during mitral valve replacement may have an equal or greater impact upon postoperative left ventricular function than mitral valve replacement with preservation of the posterior chordae; however, severing either the anterior or posterior chordae appears to be detrimental.

Restoration of left ventricular systolic performance after reattachment of the mitral chordae tendineae. The importance of valvular-ventricular interaction.

Clinical studies suggest that chorda-sparing mitral valve replacement techniques are associated with superior postoperative outcome, and several animal experiments have shown that disruption of the mitral subvalvular apparatus is followed by deterioration of left ventricular systolic function. One essential element, however, underlying the importance of chordal integrity for left ventricular function remains unproved: All investigators heretofore have been unable to demonstrate that left ventricular systolic performance can be restored by chordal reattachment after disruption of annular-papillary continuity. Therefore, we studied the effects of chordal detachment and subsequent chordal reattachment on left ventricular systolic performance using an in situ, isovolumic heart preparation in 10 halothane-anesthetized swine. The slope and left ventricular volume intercept of the isovolumic peak pressure-volume relationship were measured to assess global left ventricular systolic performance independent of load. Coronary perfusion pressure was maintained constant (95 +/- 6 mm Hg [+/- standard deviation]), and heart rates were in the physiologic range (133 +/- 26 min-1). Slope changed significantly (repeated measures analysis of variance, p = 0.0002), decreasing by 29% (from 4.74 +/- 0.94 to 3.37 +/- 0.87 mm Hg/ml, p less than 0.001) after chordal detachment and then returning to baseline (6.05 +/- 2.38 mm Hg/ml, p = 0.001) after chordal reattachment. Slope after chordal reattachment was not significantly different from the baseline value (p = 0.074). Volume intercept did not change significantly (p = 0.44) at any time. We conclude that the acute decrease in left ventricular contractility associated with surgical interruption of annular-ventricular continuity can, in fact, be reversed by chordal reattachment in this experimental model (isovolumically contracting normal porcine hearts). These data provide concrete confirmation of the concept of valvular-ventricular interaction; if these findings can be corroborated in the dilated, human left ventricle, such would strongly support efforts to preserve the mitral chordae tendineae during clinical mitral valve replacement to optimize postoperative left ventricular function.

Acute renal failure following cardiac surgery.

In a prospective 6 month study of 204 patients requiring cardiac operations, five (2.5 percent) developed acute renal failure (ARF) and five (2.5 percent) had documented renal dysfunction (RD). Preoperative left ventricular dysfunction and prolonged cardiopulmonary bypass (CPB) were important predictors of subsequent RD/ARF; CPB pressure per se was not. Physiological and clinical studies in 51 selected patients studied over an 18 month period documented the effectiveness of low flow, low pressure CPB in preserving postoperative renal function. Twenty-two patients with nonazotemic postoperative courses demonstrated moderate depression of cardiac function while the glomerular filtration rate (GFR) was normal (98 +/- 30 ml./min/1.73 M.2) within 24 hours of operation. Seventeen high risk patients developed AFF (65 percent mortality rate) and 12 experienced severe RD without ARF (17 percent mortality). ARF (65 percent mortality rate) and 12 experienced severe RD without ARF (17 percent mortality). Eleven patients with ARF and 11 with RD were studied in the early postoperative period; at this time, all 22 patients demonstrated RD with equivalent severe depression of cardiac and renal function. Superposition of further hemodynamic or toxic insults upon ischemic kidneys was usually necessary for ARF to occur.

Physiologic role of the mitral apparatus in left ventricular regional mechanics, contraction synergy, and global systolic performance.

In animal models, severing the chordae tendineae of the mitral valve reduces the maximum global left ventricular elastance (Emax,g), a load-independent measure of left ventricular systolic performance; moreover, chamber geometry is altered with systolic bulging in the region of the papillary muscle insertions. This suggests that forces transmitted by the mitral apparatus increase the regional volume elastance (Emax,r) of segments subtending the insertions of the papillary muscles, and these regions contribute substantially to overall left ventricular systolic function (Emax,g). To test this hypothesis, we developed a method to evaluate changes in the magnitude and uniformity of Emax,r as quantitated by the slopes (E'max,i) of regional left ventricular isovolumetric pressure-dimension relations. Such measurements were obtained before and after all chordal attachments of the mitral valve were surgically divided in seven open-chest swine preparations. Significant declines in E'max,i were limited to the region of the posteromedial papillary muscle insertion. Although the mean E'max,i of all ventricular regions (E'max,ave) was unchanged, regional left ventricular elastances were less uniform after the mitral chordae tendineae were severed, which indicated a less synergistic contraction, and Emax,g fell by 21% from 7.1 +/- 2.0 to 5.6 +/- 1.2 mm Hg/ml (p less than 0.05). These data demonstrate that the mitral apparatus contributes importantly to the magnitude and uniformity of regional left ventricular elastances and suggest that such alterations in regional mechanics underlie the deterioration in global left ventricular systolic performance (Emax,g) after excision of the mitral apparatus.

Long-term hemodynamics following combined heart and lung transplantation in primates.

To assess the long-term hemodynamic consequences of combined heart and lung transplantation, we investigated six rhesus monkeys 2.6 to 4.6 years (mean 4.0) after operation. Total follow-up was 24.0 primate-years. Autotransplantation had been carried out in four animals and allotransplantation in two, and the hemodynamic results were compared with those in three normal monkeys of similar size. Each animal underwent simultaneous right and left heart catheterization and pulmonary arteriography. Hemodynamic measurements were made at three levels of inspired oxygen. Arterial oxygen tension was within normal limits in all animals, and pulmonary artery pressure and pulmonary vascular resistance index did not change significantly with changes in the levels of inspired oxygen. Indices of left ventricular systolic function were normal in all animals. Values for pulmonary artery pressure and pulmonary vascular resistance index were similar in the autograft and normal groups: in the allograft group, the average pressure was 30/17 mm Hg (mean 24) and the index was 5.6 units . m2--both levels significantly higher than normal (pressure was 16/10 mm Hg, mean 13, [p less than 0.001] and index was 2.5 units . m2 [p less than 0.02]). Pulmonary arteriography in the allograft group with the highest pulmonary vascular resistance index (6.1 units . m2) was compatible with pulmonary vascular disease. Pulmonary arteriograms in the remaining eight monkeys were normal. Prolonged survival following combined heart and lung transplantation is possible in primates. Autotransplantation (and probable persisting denervation of the cardiopulmonary axis) does not necessarily result in abnormal long-term hemodynamics. The elevation in pulmonary artery pressure and pulmonary vascular resistance index in the allograft group may be related to previous episodes of pulmonary rejection, infection, or drug reaction.

Effects of the pericardium on left ventricular diastolic filling and systolic performance early after cardiac operations.

To determine whether closure of the pericardium after cardiac operations affects the filling characteristics and systolic performance of the left ventricle, we measured left ventricular volume, pressure, cardiac index, and stroke work index in 10 patients between 11 and 15 hours after cardiac operations, with the pericardium first closed and then open. At the time of operation, radiopaque tantalum markers were inserted in the left ventricular myocardium to outline the chamber in the 30-degree right anterior oblique projection, and the pericardium was closed by a continuous polypropylene suture exteriorized at both ends of the sternotomy. The patient was then transferred to the surgical intensive care unit, where left atrial pressure was measured via a fluid-filled catheter, left ventricular pressure with a micromanometer-tipped catheter, and myocardial oxygen consumption via a coronary sinus catheter. Left ventricular volume was measured by computer-aided analysis of fluoroscopic images (recorded at 30 frames per second) of the implanted myocardial markers. Left atrial pressure was maintained at target values of 10, 15, and 20 mm Hg by intravenous augmentation of blood volume. Left ventricular and left atrial pressures and volumes were measured with the pericardium closed; the pericardium was then opened by withdrawal of the pericardial suture. Radiopaque clips on the pericardial edges confirmed opening of the pericardium seconds after withdrawal of the suture. Repeated measurements of left ventricular pressures and volumes were then made at the target left atrial pressures with the pericardium open. End-diastolic volume index, peak positive time derivative of pressure, stroke work index, and cardiac index all increased significantly when the pericardium was opened (p < 0.001). Thus we found the following: (1) At physiologic pressures, the pericardium had a significant constraining effect on diastolic filling of the left ventricle, and (2) opening of the pericardium resulted in increased cardiac index and stroke work index. These increases may be attributed to the Frank-Starling response to increased left ventricular preload. The demonstrated improvement in left ventricular systolic performance should be considered when contemplating closure of the pericardium after cardiac operations, especially in patients with preoperative left ventricular dysfunction.

Left ventricular mechanics and energetics in the dilated canine heart: acute versus chronic mitral regurgitation.

The effects of volume overload associated with mitral regurgitation on left ventricular systolic mechanics, energetics, mechanical to external stroke work efficiency, and ventriculoarterial coupling were examined in 11 conscious, closed-chest dogs. Miniature radiopaque tantalum markers were implanted into the myocardium to measure left ventricular volume, and biplane cinefluoroscopic images were obtained 1 week and 3 months after creation of mitral regurgitation. Echocardiographically determined left ventricular mass increased from 116 +/- 28 to 152 +/- 29 gm (p less than 0.001). Left ventricular end-diastolic and end-ejection volumes increased by 24% and 27%, respectively. Global left ventricular systolic performance was assessed by the slopes (linear regression) of the end-systolic pressure-volume and end-systolic stress-volume relationships corrected for change in end-diastolic volume; normalized end-systolic pressure-volume relationships fell by 36% (p less than 0.001), and normalized end-systolic stress-volume relationships declined by 21% (p less than 0.005). The normalized end-systolic volume at 100 mm Hg end-systolic left ventricular pressure increased from 0.63 to 0.75 (p less than 0.05). Similar results were observed based on a nonlinear (quadratic) fit of the end-systolic pressure-volume data. In terms of energetics, the slopes of the stroke volume-end-diastolic volume and pressure-volume area-end-diastolic volume relationships fell significantly, indicating reduced external stroke work and mechanical energy at any given level of preload. Additionally, the efficiency of energy transfer from pressure-volume area to external pressure-volume work at matched end-diastolic volume was 25% lower (p = 0.006) at 3 months compared with the 1-week measurements. While overall effective arterial (or total vascular) elastance tended to decrease after a period of time, the effective ventriculovascular coupling ratio increased from 1.6 +/- 0.6 to 2.7 +/- 1.1 (p less than 0.005), indicating a greater degree of mismatch between the left ventricle and the total (forward and regurgitant) vascular load. Therefore the low pressure-volume overload of mitral regurgitation not only resulted in depressed left ventricular systolic mechanics but also was associated with deterioration of global left ventricular energetics and efficiency and exacerbated mismatch in coupling between the left ventricle and the systemic arterial bed and left atrium.

Annuloplasty with flexible or rigid ring does not alter left ventricular systolic performance, energetics, or ventricular-arterial coupling in conscious, closed-chest dogs.

Eighteen dogs were randomly chosen to undergo mitral annuloplasty with either a Carpentier-Edwards rigid ring (n = 6 in each group) or a Duran-Medtronic flexible ring or to undergo a sham procedure with an operation, but no ring. Tantalum markers were inserted to measure left ventricular volume and geometry. After 1 and 6 weeks, biplane videofluoroscopic images were obtained during steady-state conditions and during vena caval occlusion. Global and regional systolic function was assessed with load-insensitive indexes. Comparison of all three groups and both times (1 and 6 weeks) showed no significant differences among the three groups in global or regional (basal, equatorial, and apical) left ventricular systolic performance. Furthermore, neither type of annuloplasty ring significantly affected left ventricular pump efficiency, ventricular-arterial coupling ratio, or systolic circumferential contraction and rotation of the basal left ventricular sites.

Control of myocardial performance early after open-heart operations by vasodilator treatment.

The hemodynamic effects of vasodilator treatment (afterload reduction) with nitroprusside at a constant heart rate were studied in 24 patients early after aorta-coronary bypass grafting. In 12 patients, dose-response relationships were determined. Graded incremental infusions of nitroprusside produced progressive decreases in mean arterial pressure (MAP), right and left atrial pressures, and stroke work index. Stroke volume index and cardiac index rose significantly until MAP was reduced below the range of 80 to 90 mm. Hg, and then they fell to base-line levels owing to insufficient preload. In an additional 12 patients, MAP was reduced with nitroprusside to the range of 80 to 90 mm. Hg, and left atrial pressure was then restored to base-line levels during continued vasodilator administration. This sequence resulted in further augmentation of stroke volume index to a level higher than that produced by nitroprusside alone. We conclude from this investigation that nitroprusside is a clinically useful agent for primary or adjunctive therapy of mild-to-moderate low cardiac output states immediate postoperatively and that simultaneous regulation of left ventricular preload and after load during its administration is necessary in order to achieve maximal hemodynamic benefit.

Results of operations for ventricular tachycardia in 105 patients.

Operations to treat ventricular tachycardia refractory to antiarrhythmic drugs were performed in 105 patients. Intraoperative epicardial activation sequence maps were completed in 83% and endocardial maps in 57%. Mapping could be used to guide 79% of operations. When no useful mapping data were obtained, patients had visually guided antiarrhythmic operations (17%) or conventional cardiac operations (4%). The most frequently performed antiarrhythmic procedures, alone or in combination, were endomyocardial resection (45%), cryothermal destruction (44%), and encircling procedures (20%). Operative mortality was 16%, including 6% from heart failure and 4% from ventricular tachycardia. Emergency operation (p = 0.002) and New York Heart Association heart failure class (p = 0.01) were independent preoperative risk factors for cardiac operative mortality in the 98 patients with coronary artery disease. At postoperative electrophysiologic study performed in 79 patients, ventricular tachycardia could not be induced in 75% of patients who had map-guided operations and 36% who had visually guided ones (p = 0.001). During follow-up of 23 +/- 21 months, results of postoperative electrophysiologic study predicted ventricular tachycardia recurrence. At 2 years the actuarial incidence of freedom from arrhythmia recurrence was 50% +/- 10% in patients with and 78% +/- 6% in patients without inducible ventricular tachycardia (p = 0.001); it was 71% +/- 5% in patients who had map-guided operations and 37% +/- 12% in patients who had visually guided ones (p = 0.004). Ventricular tachycardia recurrence was infrequent in survivors of map-guided operations; benefits of surgical treatment for ventricular tachycardia were limited by high operative mortality and frequent arrhythmia recurrence when no useful mapping data were obtained.

The mechanisms of ventricular tachycardia in humans determined by intraoperative recording of the electrical activation sequence.

We recorded ventricular activation sequence during ventricular tachycardia in 76 patients who underwent surgical therapy of refractory ventricular tachycardia. Ventricular tachycardia arose from a discrete site (focal origination) in 28 patients (37%) or resulted from reentry around scar (macroreentry) in 22 patients (29%). The mechanism responsible for ventricular tachycardia was not discernable in the remaining 26 patients (34%), usually because of inadequacy of activation data. We conclude: (1) although focal originating of ventricular tachycardia is common, more frequently the mechanism is either macroreentry or uncertain, as assessed by conventional recording techniques; thus, a search for the "site of earliest activation" during ventricular tachycardia frequently may fail to direct rationally the operative procedure; (2) conventional techniques for intraoperative study of electrical activation during ventricular tachycardia are inadequate.