The activity of the adrenergic system plays an important role in the genesis of malignant arrhythmias and the spreading of the infarcted zone in acute myocardial ischemia. Acute myocardial ischemia induces an increased activity of adenylyl cyclase. This sensitization at the enzyme level as shown in the isolated perfused rat heart occurs rapidly after the onset of ischemia (5-15 minutes) and is rapidly reversible on reperfusion. With prolonged ischemia, it is only transient and is followed by a gradual loss of the adenylyl cyclase activity. The increased activity of adenylyl cyclase is even retained after partial purification, suggesting a covalent modification of the enzyme. Blockade of alpha 1-adrenergic receptors does not prevent this sensitization, demonstrating that it occurs independently of alpha 1-adrenergic receptor activation. Only blockade of protein kinase C by various inhibitors, such as polymyxin B or staurosporine, is able to completely prevent this sensitization process. Moreover, in acute myocardial ischemia an activation of protein kinase C could be identified using its translocation from the cytosol to the particulate fraction as an indicator. Blockade of alpha 1-adrenergic receptors using prazosin fails to prevent the activation of protein kinase C and consequently the sensitization of the adenylyl cyclase system, indicating that the ischemia-induced translocation of protein kinase C occurs independently of alpha 1-adrenergic receptors. These data characterize for the first time an important interaction of two effector enzymes of two distinct signal transduction pathways, i.e., the adenylyl cyclase system and the protein kinase C system in acute myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

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Sentinel lymph node biopsy (SNB), using radioactive tracers, is a novel, interesting tool in the staging of patients with oral and oropharyngeal squamous-cell carcinoma (OOSCC), which could lead to a reduced rate of elective neck dissections. The aim of the study was to evaluate the ranking of measured radioactivity in the sentinel lymph nodes (SLNs) and to correlate these findings with histopathological results to assess the number of SLN being sufficient for exact staging of the neck. In 77 consecutive patients with T1-4 OOSCC clinically and positron emission tomography-staged N0, between 15 and 55 MBq of Tc- 99m-labeled albumin-microcolloids were injected peritumorally and 213 SLNs were excised by small skin incisions using a gamma probe 2-3 hours later. The counts per second (cps) were measured ex vivo and excised SLNs were ranked according to their cps defining the LN with the highest activity as primary SLN, followed by a 2nd, 3rd, and so forth, SLN. Elective neck dissections were not performed. Median activity was 213 cps. All levels harbored SLNs with a maximum (43%) in level II and a minimum in level V (1%). SLNs in level II had significantly higher tracer accumulation (median, 289 cps) than those in levels I (144 cps) and IV (149 cps), but distant levels did not have significantly lower counts, compared to proximal. Eight (8) pathologically positive SLNs in 7 patients (7/77 = 9%; median activity, 157 cps) were detected. The median counts of the positive SLNs were not significantly different from those of the 205 negative SLNs (235 cps). The positive SLN was the one with the highest tracer accumulation in 4 cases, with the second highest in 1 case, and with the third highest tracer accumulation in 2 cases. Three (3) positive SLN were in level IB, 4 in level IIA, and 1 in level III. One (1) patient had 2 positive SLNs: a SLN with the third highest activity in level IIB and a SLN with the fifth highest activity in level III. In OOSCC, excision of only 1 SLN is not feasible. The positive SLNs were not necessarily the hottest nodes. Utilizing radiotracer lymphatic mapping, the 3 SLNs with the highest activity should be excised for exact staging of the neck in patients with T1-3 tumors. Excision of all radioactive nodes is recommended until further studies will prove this result. Large T4a tumors should not be staged using SNB.

As a staging tool for N0 necks and T1-3 tumors, SNB could lead to a considerable reduction in the number of elective NDs. It could be well integrated into a multi-modal treatment scheme.