Microvascular hemodynamics in human hypothermic circulatory arrest and selective antegrade cerebral perfusion.

OBJECTIVE: The behavior of the human microcirculation in the setting of cardiac arrest is largely unknown. Animal experiments have consistently revealed that global hemodynamics do not necessarily reflect microvascular perfusion. In addition, the time it takes for capillary blood flow to stop after the heart arrests is debated. Estimations range from 50 seconds to 5 mins, but data in humans are lacking. Aortic arch surgery frequently necessitates deep hypothermic circulatory arrest and subsequent selective antegrade cerebral perfusion. To elucidate microvascular behavior surrounding cessation of human circulation, we used sublingual microvascular imaging in this setting. DESIGN: Prospective, observational study. SETTING: Operating room of a large tertiary referral center for cardiac surgery. PATIENTS: Seven patients undergoing elective aortic arch repair. INTERVENTIONS: We used sidestream dark field imaging to study the sublingual microcirculation immediately before circulatory arrest, during circulatory arrest, and immediately after selective antegrade cerebral perfusion. MEASUREMENTS AND MAIN RESULTS: Results are reported as mean (sd) unless indicated otherwise. Before circulatory arrest, perfused vessel density was 6.41 (1.18) for small (<20 microm) and 1.57 (0.88) mm for large (>20 microm) microvessels. Microvascular flow index was a median of 3.0 (interquartile range 3.0-3.0) for both vessel sizes. After circulatory arrest, there was no equilibration of arterial and venous blood pressure before onset of selective antegrade cerebral perfusion after 59 (17) secs (range, 40-80 secs). Flow in small microvessels came to a complete stop after 45 (9) secs (range, 34-57 secs) after transition to circulatory arrest. However, flow in larger microvessels did not completely stop before selective antegrade cerebral perfusion started. Selective antegrade cerebral perfusion restored microvascular flow, reaching precirculatory arrest levels after 45 (27) secs (range, 20-85 secs). CONCLUSIONS: In a controlled surgical setting, circulatory arrest in humans induces a complete sublingual small microvessel shutdown within 1 min. However, flow in larger microvessels persists. Selective antegrade cerebral perfusion was able to restore microvascular flow to precirculatory arrest levels within a similar timeframe.

Isolated lung perfusion for pulmonary metastases, a review and work in progress.

Pulmonary metastasectomy is a widely accepted treatment for many patients with pulmonary metastases from various solid tumors. Nevertheless, 5-year survival is disappointing, with rates of 25-40%, and many patients develop recurrences. Isolated lung perfusion (ILuP) is a promising new technique to deliver high-dose chemotherapy to the lungs, while minimising systemic toxicities. This procedure is technically safe and feasible; however, clinical value and efficacy remain unclear. The aim of this paper is to give a review of literature on ILuP in humans, and to describe the development of the perfusion procedure in our institute.

Isolated lung perfusion with melphalan for resectable lung metastases: a phase I clinical trial.

BACKGROUND: Current 5-year survival after complete resection of pulmonary metastases is 20% to 40%, and many patients develop intrathoracic recurrences. Isolated lung perfusion is an experimental technique to deliver high-dose chemotherapy to the lung without systemic exposure. A phase I trial of isolated lung perfusion with melphalan (MN) combined with pulmonary metastasectomy for resectable lung metastases was conducted to define the dose-limiting toxicity and maximum tolerated dose. METHODS: From May 2001 to August 2003, 16 patients underwent isolated lung perfusion with MN, followed by surgical resection of lung metastases. Patients were treated with increasing MN doses (15, 30, 45, and 60 mg). For each dose level, normothermia (37 degrees C) and hyperthermia (42 degrees C) were evaluated (n = 3 per level). Serum samples were obtained during the procedure. Pulmonary, hematologic, and nonhematologic toxicities were recorded. The primary tumor was colorectal in 7 patients, renal in 5, sarcoma in 3, and salivary gland in 1. Isolated lung perfusion was performed unilaterally in 11 patients, and staged bilaterally in 5. RESULTS: In total, 21 procedures of isolated lung perfusion with complete metastasectomy were performed without technical difficulties. Operative mortality was 0%, and no systemic toxicity was encountered. Grade 3 pulmonary toxicity developed at a dose of 60 mg of MN at 37 degrees C in 2 of 3 patients at this dose, terminating the trial. CONCLUSIONS: Isolated lung perfusion with MN combined with pulmonary metastasectomy is feasible. Dose-limiting toxicity occurred at a dose of 60 mg of MN at 37 degrees C, and the maximum tolerated dose was set at 45 mg of MN at 42 degrees C.