Peter Van Trigt

Coronary artery bypass in patients with severely depressed ventricular function

This study evaluates whether patients with coronary artery disease and severely depressed left ventricular ejection fraction benefit from coronary artery bypass grafting. From 1981 to 1991, 118 consecutive patients with ejection fraction less than or equal to 0.25 underwent isolated coronary artery bypass grafting at Duke University Medical Center. Operative mortality was 11%. Ventricular arrhythmia requiring treatment was the most common postoperative complication (27%), followed by low cardiac output state (22%). Median length of postoperative hospitalization was 9 days. Kaplan-Meier estimate of survival at 1 year and 5 years was 77.2% and 57.5%, and was better than estimated survival with medical therapy alone. Survivors experienced significant improvement in angina class (p < 0.0001), congestive failure class (p < 0.0001), and follow-up ejection fraction (p < 0.005). Of 22 preoperative factors evaluated by univariate survival analysis, five were associated with significantly greater mortality: other vascular disease (p < 0.005), female sex (p < 0.005), hypertension (p < 0.005), elevated left ventricular end-diastolic pressure (p < 0.05), and depressed cardiac index (p < 0.05). Considering length of hospitalization, three factors showed significant adverse effect in a multivariate Cox model: time on cardiopulmonary bypass (p < 0.005), acute presentation (p < 0.005), and female sex (p < 0.01). These data and review of the literature suggest that patients with coronary artery disease and severely depressed ejection fraction benefit from coronary artery bypass grafting, and specific preoperative factors may help determine optimal treatment.

Milrinone Improves Pulmonary Hemodynamics and Right Ventricular Function in Chronic Pulmonary Hypertension

BACKGROUND Right ventricular failure after cardiac transplantation is commonly related to preexisting recipient pulmonary hypertension. This study was designed to investigate the effects of intravenous milrinone on pulmonary hemodynamic indices and right ventricular function in a canine model of monocrotaline pyrrole-induced chronic pulmonary hypertension. METHODS Eight mongrel dogs underwent pulmonary artery catheterization to measure right-sided hemodynamic indices before and 6 weeks after a right atrial injection of monocrotaline pyrrole. Six weeks after injection, all hearts were instrumented with a pulmonary artery flow probe, ultrasonic dimension transducers, and micromanometers. Data were collected at baseline and after milrinone infusion. RESULTS Six weeks after monocrotaline pyrrole injection, significant increases in the pulmonary artery pressure and pulmonary vascular resistance were observed. Milrinone led to significant increases in right ventricular function as well as significant improvements in pulmonary vascular resistance, pulmonary blood flow, and left ventricular filling. CONCLUSIONS This investigation demonstrates the well-known hemodynamic and inotropic effects of milrinone which, in the setting of monocrotaline pyrrole-induced pulmonary hypertension, were also associated with significant increases in pulmonary blood flow and left ventricular filling.

Pharmacological Strategies for Improving Diastolic Dysfunction in the Setting of Chronic Pulmonary Hypertension

BACKGROUND Right ventricular (RV) hypertrophy is an adaptive process that occurs in the setting of chronic pulmonary hypertension (CPH) and can lead to alterations in normal RV diastolic properties. This study was designed to investigate the effects of NO and milrinone on RV diastolic dysfunction in the setting of CPH and RV hypertrophy by use of a canine model of monocrotaline pyrrole (MCTP)-induced CPH. METHODS AND RESULTS Sixteen mongrel dogs (22 to 24 kg) were used. Animals underwent percutaneous pulmonary artery (PA) catheterization to measure pulmonary hemodynamics before and 8 weeks after injection of 3 mg/kg MCTP (n=8) or placebo (control, n=8). Eight weeks after injection, all hearts were instrumented with a PA flow probe, sonomicrometric dimension transducers, and micromanometers. Data were collected at baseline and after both NO and milrinone administration. Diastolic properties were quantified by use of the end-diastolic pressure-volume relationship and the time constant of ventricular isovolumic relaxation. Eight weeks after injection, significant increases in the PA pressure and pulmonary vascular resistance were observed in MCTP dogs. Significant worsening of RV diastolic function occurred in association with significant increases in the ratio of RV dry weight to LV+septal dry weight. NO and milrinone administration both led to significant improvements in RV diastolic properties. CONCLUSIONS In the setting of MCTP-induced CPH, significant worsening of RV diastolic function was observed in association with significant increases in the ratio of RV dry weight to LV+septal dry weight, suggesting that these changes are partially due to RV hypertrophy. The significant improvement in RV diastolic properties after both NO and milrinone administration suggests that these agents may be effective forms of pharmacological therapy for improving RV diastolic dysfunction in the setting of CPH.

Physiologic Effects Of Extracellular Superoxide Dismutase Transgene Overexpression On Myocardial Function After Ischemia And Reperfusion Injury

OBJECTIVE Myocardial injury after ischemia and reperfusion may be mediated, in part, by oxygen-derived free radicals. In this study the protective effects of extracellular superoxide dismutase overexpression were directly assessed in the hearts of transgenic mice, after ischemia and reperfusion injury, using an isolated work-performing murine heart preparation and computerized analysis of functional data. METHODS A blinded study was performed to compare cardiac function in the hearts of both transgenic mice with a 3.5-fold overexpression of myocardial extracellular superoxide dismutase (n = 6, 22 to 26 gm) and littermate controls (n = 8, 22 to 26 gm). Preload-dependent cardiac output, contractility, heart rate, stroke work, and stroke volume were evaluated in the two groups before and after a 6-minute period of normothermic ischemia. RESULTS No differences were found between extracellular superoxide dismutase hearts and control hearts in any parameter of myocardial function before ischemia. After ischemia, decreases in cardiac output occurred in both groups; however, this decrease was larger in control mice compared with extracellular superoxide dismutase mice. A higher percentage of recovery was also observed in the contractility, heart rate, stroke work, and stroke volume of extracellular superoxide dismutase hearts compared with control hearts. CONCLUSION After global normothermic ischemia and subsequent reperfusion, decreases in cardiac function occurred in both extracellular superoxide dismutase and control mice; however, a higher percentage of recovery was observed in the extracellular superoxide dismutase overexpressed hearts. These data suggest that extracellular superoxide dismutase transgene overexpression significantly improves preservation of myocardial function after ischemia and reperfusion injury.

Myocardial β-Adrenergic Receptor Function and High-Energy Phosphates in Brain Death– Related Cardiac Dysfunction

BACKGROUND Cardiac failure remains an important problem after heart transplantation and may be associated with events that occur during brain death (BD) before transplantation. In this study, cardiac function is studied after BD, and biochemical evaluation of myocardial high-energy phosphates and the beta-adrenergic receptor system is presented. METHODS AND RESULTS The hearts of 17 mongrel dogs (23 to 31 kg) were instrumented with flow probes, micromanometers, and ultrasonic dimension transducers to measure ventricular pressure and volume relationships. In a validated canine BD model, systolic right and left ventricular (RV/LV) function was analyzed by load-insensitive measurements during caval occlusion (preload-recruitable stroke work, PRSW). The beta-adrenergic receptor (BAR) density, adenylate cyclase (AC) activity, and myocardial ATP and creatine phosphate (CP) were measured before and 6 to 7 hours after BD. Results are expressed as mean +/- SEM (*P < .05 versus baseline, paired two-tailed Students t test). Myocardial function deteriorated significantly from baseline PRSW (RV, 22 +/- 1 erg x 10(3); LV, 75 +/- 4 erg x 10(3)) by 37 +/- 10% for the RV (P < .001) and 22 +/- 7% for the LV (P < .001). BAR density increased from 282 +/- 42 to 568 +/- 173 fmol/mg for the RV and from 291 +/- 64 to 353 +/- 56 fmol/mg for the LV. Isoproterenol-stimulated AC activity was also significantly enhanced after BD. ATP and CP, however, remained unchanged after BD compared with baseline values before BD. CONCLUSIONS BD causes significant systolic biventricular dysfunction. The loss of ventricular function after BD was more prominent in the right ventricle and may contribute to early postoperative RV failure in the recipient. These injuries occurred despite BAR system upregulation after BD. Global myocardial ischemia is unlikely, since ATP and CP remained normal before and after BD.

Right ventricular dysfunction after cardiac transplantation: primarily related to status of donor heart

BACKGROUND It is unclear whether right ventricular dysfunction after transplantation is due to donor brain death-related myocardial injury or recipient pulmonary hypertension. METHODS A canine donor model of brain death and a monocrotaline pyrrole-induced chronic pulmonary hypertension recipient model were established, and used for 30 orthotopic bicaval cardiac transplantations divided into three groups: Controls (group A, normal donor/recipient), group B (brain-dead donors/normal recipient), and group C (normal donor/recipients with pulmonary hypertension). Right ventricular function was measured before transplant and brain death, 4 hours after brain death, and after transplant (1 hour off bypass) by load-independent means plotting stroke work versus end-diastolic volume during caval occlusion. Right ventricular total power and pulmonary vascular impedance were determined by Fourier analysis. RESULTS In comparison to the control group right ventricular preload-recruitable stroke work and total power decreased significantly after brain death and transplant in group B (from 22.7 x 10(3) erg (+/-1.2) at baseline to 15.6 x 10(3) (+/-0.9) after brain death and to 11.3 x 10(3) (+/-0.9) after transplant). In group C there was a significant increase in pulmonary artery pressure, impedance, right ventricular preload-recruitable stroke work, total power after transplant. CONCLUSIONS Normal donor hearts adapt acutely to the recipients elevated pulmonary vascular resistance by increasing right ventricular power output and contractility. Brain death caused significant right ventricular dysfunction and power loss, which further deteriorated after graft preservation and transplantation. The effects of donor brain death on myocardial function contribute to right ventricular dysfunction after cardiac transplantation.

Swine lungs expressing human complement–regulatory proteins are protected against acute pulmonary dysfunction in a human plasma perfusion model

UNLABELLED Pulmonary transplantation is currently limited by the number of suitable cadaver donor lungs. For this reason, pulmonary xenotransplantation is currently being investigated. OBJECTIVE Our goal was to assess the role of complement in pulmonary xenograft dysfunction. METHODS The pulmonary function of swine expressing human decay accelerating factor and human CD59 (n = 6) was compared with that of the lungs from nontransgenic (control) swine (n = 6) during perfusion with human plasma. RESULTS After 2 hours of perfusion, the pulmonary vascular resistance was 1624 +/- 408 dynes.sec.cm-5 in control lungs and 908 +/- 68 dynes.sec.cm-5 in transgenic lungs (p < 0.05). Control lungs had a venous oxygen tension of 271 +/- 23 mm Hg with a ratio of venous oxygen tension to inspired oxygen fraction of 452 +/- 38 at 2 hours of perfusion; transgenic lungs had a venous oxygen tension of 398 +/- 11 mm Hg and a ratio of venous oxygen tension to inspired oxygen fraction of 663 +/- 18 (p < 0.05). Control lungs showed a decrease of 79.8% +/- 3.7% in static pulmonary compliance by 2 hours, versus a 12.0% +/- 8.1% decrease by the transgenic lungs (p < 0.05). The control lungs also developed 561.7 +/- 196.2 ml of airway edema over 2 hours, in contrast to 6.5 +/- 1.7 ml in transgenic lungs (p < 0.05). CONCLUSION Lungs from swine expressing human decay accelerating factor and human CD59 functioned better than nontransgenic swine lungs when perfused with human plasma. These results suggest that complement activation is involved in producing acute pulmonary xenograft dysfunction and demonstrate that lungs from swine expressing human decay accelerating factor and human CD59 are protected against pulmonary injury when perfused with human plasma.

First successful bridge to cardiac transplantation using direct mechanical ventricular actuation.

Currently available ventricular assist devices are technically difficult to implant, require continuous anticoagulation, and are associated with hemorrhagic and thromboembolic complications. Direct mechanical ventricular actuation is a biventricular assist device that can be applied in 3 to 5 minutes through a left anterior thoracotomy and has no direct blood contact or need for anticoagulation. The present study was designed to determine the effects of direct mechanical ventricular actuation in total biventricular circulatory support. Cardiogenic shock refractory to standard therapy developed in 2 patients awaiting cardiac transplantation. Direct mechanical ventricular actuation was applied and provided immediate hemodynamic stabilization in both. All inotropic agents and intraaortic balloon support were then discontinued. Fifty-six hours of circulatory support bridged the first patient to successful cardiac transplantation without complication. The patient is alive and well more than 1 year later without incident of infection or rejection. The second patient suffered cardiac arrest and required closed chest cardiopulmonary resuscitation before device application. After 45 hours of support, it was determined that irreversible neurologic injury had occurred and direct mechanical ventricular actuation was discontinued. Neither patients native heart exhibited any histologic evidence of device-related trauma. Direct mechanical ventricular actuation has undergone limited clinical investigation since its original description 25 years ago, but in these initial trials, the device has proved effective. The concept of mechanically actuating the ventricles appears to be a valuable, yet under-utilized method of total circulatory support.

Cytomegalovirus Pericarditis: A Case Series and Review of the Literature

Cytomegalovirus (CMV) commonly infects both normal and immunocompromised hosts. Although it usually produces an asymptomatic infection to mild illness, CMV has the potential to significantly injure many different organs. Reports of CMV causing pericardial disease, however, are limited and documentation of infection by growth of the virus from tissue or fluid is rare. As part of a prospective trial of subxiphoid pericardial biopsy in 57 adult patients with large pericardial effusions, three culture-proven cases and one serologically confirmed case of CMV pericardial disease were discovered. Subsequently, CMV was grown from the pericardium of an infant with congenital heart disease. A review of the documented cases of CMV pericarditis is provided along with a discussion of the pathogenesis and significance of this perhaps not so uncommon disease.

Effects of standard mitral valve replacement on left ventricular function

Recent studies have suggested that excision of the mitral valve apparatus during mitral valve replacement impairs left ventricular performance. However, functional measurements in humans have been difficult to obtain in a load-independent fashion. To investigate this concept, 12 patients (mean age, 65 +/- 8 years; mean New York Heart Association functional class, 3.3 +/- 0.7) with 4+ mitral regurgitation (n = 8) or mitral stenosis (valve area, 1.2 +/- 0.2 cm2) (n = 4) underwent prosthetic valve replacement using crystalloid cardioplegia. No patient required therapeutic inotropic support, every patient had at least the anterior mitral leaflet excised, and paced heart rate was maintained constant throughout. Left ventricular volume was measured with radionuclide angiocardiography, left ventricular pressure with a 3F micromanometer, and left ventricular wall volume with two-dimensional transesophageal echocardiography. Left ventricular preload was varied over a mean end-diastolic pressure range of 9 to 20 mm Hg and an end-diastolic volume range of 134 to 170 mL to generate four to five steady-state pressure-volume loops before and ten minutes after cardiopulmonary bypass. Left ventricular performance was estimated with the stroke work/end-diastolic volume relationship, which is insensitive to load. After bypass, no significant change (p greater than 0.1) was noted in wall volume for patients with mitral regurgitation or mitral stenosis (175 +/- 68 to 189 +/- 63 mL/m2 and 130 +/- 22 to 127 +/- 19 mL/m2, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)