Dennis L. Modry

Long-Term Treatment With Oral Sildenafil Is Safe and Improves Functional Capacity and Hemodynamics in Patients With Pulmonary Arterial Hypertension

Background—The prognosis and functional capacity of patients with pulmonary arterial hypertension (PAH) is poor, and there is a need for safe, effective, inexpensive oral treatments. A single dose of sildenafil, an oral phosphodiesterase type-5 (PD-5) inhibitor, is an effective and selective pulmonary vasodilator in PAH. However, the long-term effects of PD-5 inhibition and its mechanism of action in human pulmonary arteries (PAs) are unknown. Methods and Results—We hypothesized that 3 months of sildenafil (50 mg orally every 8 hours) added to standard treatment would be safe and improve functional capacity and hemodynamics in PAH patients. We studied 5 consecutive patients (4 with primary pulmonary hypertension, 1 with Eisenmenger’s syndrome; New York Heart Association class II to III). Functional class improved by ≥1 class in all patients. Pretreatment versus posttreatment values (mean±SEM) were as follows: 6-minute walk, 376±30 versus 504±27 m, P <0.0001; mean PA pressure, 70±3 versus 52±3 mm Hg, P <0.007; pulmonary vascular resistance index 1702±151 versus 996±92 dyne · s · cm−5 · m−2, P <0.006. The systemic arterial pressure was unchanged, and no adverse effects occurred. Sildenafil also reduced right ventricular mass measured by MRI. In 7 human PAs (6 cardiac transplant donors and 1 patient with PAH on autopsy), we showed that PD-5 is present in PA smooth muscle cells and that sildenafil causes relaxation by activating large-conductance, calcium-activated potassium channels. Conclusion—This small pilot study suggests that long-term sildenafil therapy might be a safe and effective treatment for PAH. At a monthly cost of

A multicenter, randomized, controlled trial of Celsior for flush and hypothermic storage of cardiac allografts

492 Canadian, sildenafil is more affordable than most approved PAH therapies. A large multicenter trial is indicated to directly compare sildenafil with existing PAH treatments.

Successful cardiac transplantation with methanol or carbon monoxide-poisoned donors.

BACKGROUND A multicenter, randomized, controlled, open-label trial was conducted to evaluate the safety and efficacy of Celsior when used for flush and hypothermic storage of donor hearts before transplantation. METHODS Heart transplant recipients were randomized to one of two treatment groups in which donor hearts were flushed and stored in either Celsior or conventional preservation solution(s) (control). Study subjects were followed for 30 days after transplantation. RESULTS A total of 131 heart transplant recipients were enrolled (Celsior, n = 64; control, n = 67). The treatment groups were evenly distributed in donor and recipient base line characteristics. Graft loss rate was lower in the Celsior group on day 7 (3% versus 9%) and on day 30 (6% versus 13%), but the difference was not statistically significant based on 95% confidence interval analysis. No significant difference was measured between the Celsior and control groups in 7-day patient survival (97% versus 94%) and the proportion of patients with one or more adverse events (Celsior, 88%; control 87%) or serious adverse events (Celsior, 38%; control, 46%). Significantly fewer patients in the Celsior group developed at least one cardiac-related serious adverse event (13% versus 25%). CONCLUSIONS Celsior was demonstrated to be as safe and effective as conventional solutions for flush and cold storage of cardiac allografts before transplantation.

Antimicrobial prophylaxis for open heart operations

BACKGROUND Patients succumbing to methanol or carbon monoxide poisoning are usually rejected for heart donation. Increasing demand for donors has lead to the expansion of acceptance criteria and increased use of the marginal donor. METHODS We transplanted hearts from donors who had had methanol intoxication in three cases and carbon monoxide exposure in two cases. Standard donor evaluation criteria and transplantation techniques were used. RESULTS All of the transplants were successful. Three of the recipients required significant inotropic support for a few days postoperatively; however, all of the hearts functioned well over the intermediate and long term. Two recipients (1 from each group) died of complications other than heart failure (1.5 and 2 years postoperatively). CONCLUSIONS Successful heart transplantation can be achieved using the hearts from patients succumbing to methanol or carbon monoxide poisoning. Routine evaluation of cardiac function and myocardial damage is adequate for screening these donors. Hearts from methanol-poisoning victims may require longer inotropic support postoperatively before complete recovery, but can provide excellent long-term function and results.

Extracorporeal life support for the control of life-threatening pulmonary hemorrhage.

Between 1986 and 1988, 450 adults undergoing coronary artery bypass, cardiac valve replacement, or both were enrolled into a prospective, randomized, comparative trial of cephalothin versus cefamandole as perioperative prophylaxis. They were assessed during their hospitalization and at 6 weeks and 6 months after discharge for postoperative infectious complications. Eleven patients had major postoperative infections including 5 with sternal wound infections (three bacteremic), 6 with bacteremia, 1 with prosthetic valve endocarditis, and 3 with severe venous donor graft site infections. Eight major infections occurred in patients receiving cephalothin prophylaxis and three in patients receiving cefamandole, with all five sternal wound infections occurring in the cephalothin group. Postoperative pathogens responsible for the major infections included gram-negative aerobes in 5 patients, Staphylococcus aureus in 4, and Staphylococcus epidermidis in 2. Preoperative colonizing staphylococcal isolates were not predictive of postoperative staphylococcal pathogens. Although there was no statistically significant difference in rate of major postoperative infectious complications using either cephalothin or cefamandole prophylaxis, there was a trend in favor of cefamandole. Gram-negative aerobes are becoming increasingly important pathogens in this setting.

Hypothermic Perfusion Preservation of the Isolated Dog Lung

Pulmonary hemorrhage is a dreadful complication after pulmonary thromboendarterectomy. We describe a novel management in which the patient is supported with active venting of the pulmonary vascular bed while on veno-arterial extracorporeal life support.

Designing an outcome-oriented computer decision-support system for cardiovascular ICU—a preliminary report

Abstract A total of 13 left lower canine pulmonary lobes were perfused with glucose-enriched autologous blood. Of these, 5 test lobes were perfused at 28°C. for periods ranging from 6 to 21 hours and were subsequently evaluated during a 1-hour period of normothermic (37°C.) perfusion. Excellent preservation of lobe function was shown by comparison with the initial normothermic perfusion interval of control lobes. Elevated pulmonary vascular resistance noted with hypothermic perfusion did not adversely affect respiratory gas exchange or compliance and may have been due to subnormal pulmonary venous pressures. In a second group of 12 dogs, 3 whole left lungs subjected to extended hypothermic perfusion exhibited normal functional adequacy following allotransplantation compared with nonpreserved controls. The salutory effect of hypothermia permitted perfusion preservation of pulmonary function and morphology for a longer period than has hitherto been reported.

Long-term outcome of lung transplantation in previous intravenous drug users with talc lung granulomatosis.

This paper describes the conceptual framework and preliminary results of an outcome-oriented decision-support system prototype for the cardiovascular intensive care unit (CVICU). The major characteristics of this design include: (1) its problem-based approach to solving clinical problems; (2) an integrated structure with the hospital information system in terms of its data, model and knowledge bases; (3) proposed alternative modes of interaction that include monitoring and critiquing; (4) and research modules that design, manage, and analyze outcome-based clinical studies. At present, an initial prototype has been implemented on a PC as a set of modules accessible from a main menu. The structural framework of the overall system is fairly well defined but only limited quantitative, statistical and expert knowledge has been captured. The second phase of the project involves porting the prototype to a Unix workstation environment, refining and adding models to the model base, expanding its knowledge bases, reasoning capability, and testing the prototype with actual clinical cases in a real-time fashion.

Endoscopic Diagnosis and Treatment of Postoperative Bronchopleural Fistula

Talc lung granulomatosis results from the intravenous use of medication intended for oral use. Talc (magnesium silicate) acts as filler in some oral medications; when injected intravenously, it deposits in the lungs leading to airflow obstruction and impaired gas exchange. Allocation of donor lungs to previous intravenous drug users is controversial. After a careful selection process, 19 patients with talc lung granulomatosis have received lung allografts in our program. Long-term survival for these patients is excellent and our results suggest the previous use of intravenous drugs should not necessarily preclude lung transplantation.