Posttraumatic stress disorder after implantation of a mechanical assist device followed by heart transplantation: evaluation of patients and partners.

AIM: We sought to investigate the prevalence of posttraumatic stress disorder, anxiety, and depression in patients and their partners after implantation of a mechanical assist device as a bridge to heart transplantation. METHODS: This was a retrospective assessment of 41 patients (age 46.3 +/- 12.0 years; male-female ratio, 38:3; time since transplantation, 55.3 +/- 34.2 months [range, 7-122 months) and 27 partners (male-female ratio 2:25) by standardized instruments (Impact of Event Scale, Hospital Anxiety and Depression Scale), in 2 University Heart Transplant Centers (Vienna, Austria, Munster, Germany). The duration of the support systems (MicroMed DeBakey-VAD in 17 patients, Novacor in 10, Thoratec in 8, TCI HeartMate in 5, and Berlin Heart Incor in 1 patient) ranged from 28 to 711 (176 +/- 146) days. RESULTS: None of the patients, but 23% of the partners (n = 6), met the criteria for posttraumatic stress disorder (Maercker cutoff >0). The Impact of Event Scale (IES) sum scales differed significantly between the 2 groups (21.2 +/- 15.1, mean +/- SD) for the patients versus 38.1 +/- 27.8 for the partners, respectively; P = .001). Two percent of the patients, but 19% of the partners, showed mild to moderate depression; 4% of patients, but 23% of their partners, reported mild to moderate anxiety. None of the results were significantly influenced by the time since transplantation, patient age, diagnoses, type of assist device, or indication for heart transplantation. CONCLUSIONS: Despite patients being much closer to a life threat, their partners experience significantly more psychologic distress even in the long run. Our findings highlight the need for attention to the supporting persons.

A growth factor mixture that significantly enhances angiogenesis in vivo.

Studies of therapeutic angiogenesis have generally focused on single growth factor strategies. However, multiple factors participate in angiogenesis. We evaluated the angiogenic potential of a growth factor mixture (GFm) derived from bovine bone. The major components of GFm (SDS-polyacrylamide gel electrophoresis, mass spectrometry, and Western blot) include transforming growth factor-beta1-3, bone morphogenic protein-2-7, and fibroblast growth factor-1. GFm was first shown to induce an angiogenic response in chorioallantoic membranes. Next, myocardial ischemia was induced in 21 dogs (ameroid) that were randomized 3 weeks later to received GFm 1 mg/ml (I), GFm 10 mg/ml (II), or placebo (P) (with investigators blinded to conditions) injected in and adjacent to ischemic myocardium. Dogs were assessed 6 weeks later using quantitative and semiquantitative measures. There were GFm concentration-dependent improvements in distal left anterior descending artery (LAD) opacification by angiography (P: 0.4 +/- 0.2, I: 1.1 +/- 0.14, II: 1.6 +/- 0.3, angiographic score p = 0.014). Histologically, there was also concentration-dependent vascular growth response of relatively large vessels (P: 0.21 +/- 0.15, I: 1.00 +/- 0.22, II: 1.71 +/- 0.18, vascular growth score p = 0.001). Resting myocardial blood flow (colored microspheres) was not significantly impaired in any group. However, maximum blood flow (adenosine) was reduced in ischemic territories and did not improve in GFm-treated hearts. GFm, a multiple growth factor mixture, is a potent angiogenic agent that stimulates large vessel growth. Although blood flow did not improve during maximal vasodilatory stress, large intramyocardial collateral vessels developed and angiographic visualization of the occluded distal LAD improved significantly. The use of multiple growth factors may be an effective strategy for therapeutic angiogenesis provided a more effective delivery strategy is devised that can achieve improved maximum blood flow potential.

Histologic evidence that basic fibroblast growth factor enhances the angiogenic effects of transmyocardial laser revascularization.

OBJECTIVES: To determine whether addition of basic fibroblast growth factor (bFGF), an angiogenic growth factor, enhances the angiogenic effects of transmyocardial laser revascularization (TMR). BACKGROUND: TMR is an investigational therapy for treating patients with medically refractory angina not amenable to traditional therapies. Histologic and blood flow studies in animals have suggested that TMR enhances angiogenesis above that normally seen in ischemic myocardium. We tested the hypothesis that bFGF administered into TMR channels further enhance the angiogenic effects of TMR. METHODS: Chronic ischemia was created in 3 groups of dogs using an ameroid constrictor on the proximal LAD. In the bFGF group (n = 5) non-transmyocardial channels were created in the LAD territory and bFGF, (100 ng/ml) dissolved in pluronic gel was injected into the each channel. In the TMR group (n = 7), transmyocardial channels were created without bFGF. A control group (n = 7) had ischemia without TMR of bFGF. 5-bromo-2'-deoxyuridine (BrdU) was administered to mark proliferating cells. After 8 weeks survival, colored microspheres were injected to assess the regional myocardial blood flow. RESULTS: TMR and TMR+bFGF increased total vascular density by approximately 40% over that observed in the control group. However, the number of large vessels (internal diameter > or = 50 microm) was doubled by the addition of bFGF, and this correlated with a 50% increase in the density of proliferating vascular cells and a tripling of the total estimated vascular cross sectional area. Blood flow to the LAD territory was increased by TMR compared to controls, with no further benefit observed in the bFGF group. CONCLUSIONS: On a histologic basis, basic fibroblast growth factor further enhances angiogenesis following TMR in ischemic myocardium mainly by increasing the size but not the total number of vessels.

An examination of potential mechanisms underlying transmyocardial laser revascularization induced increases in myocardial blood flow.

Within the past few years, transmyocardial laser revascularization (TMR) has attracted the attention of cardiologists and cardiac surgeons as a therapy for patients suffering from otherwise treatable coronary artery disease. Clinical studies have consistently shown symptomatic improvement that lasts at least 1 year in a majority of patients. The original hypothesis that prompted development of the technique was that direct myocardial perfusion from the chamber could be achieved through chronically patent channels, as is the case in reptilian hearts. Results of our early studies failed to support this hypothesis and we turned to investigations aimed at testing other possible explanations. The experiments, which are reviewed in this article, showed that TMR enhances vascular growth in ischemic myocardium.