Major branches from right and left sympathetic ganglia were electrically stimulated while force of contraction was recorded from multiple areas of the right and left ventricles. Stimulation of the stellate ganglia generally elicited alterations in force of contraction from all test segments, but excitation of selected nerve trunks induced responses in highly localized regions of the heart. Ablation of narrow strips of epicardium resulted in obliteration of contractile responses in specific, highly localized regions of the heart; thus a major fraction of the sympathetic innervation of the ventricular chambers is by way of the epicardial plexus. The anterior surface of the right ventricle is supplied by projection pathways arising within the immediately subepicardial regions of the right A-V groove and, to a lesser extent, from the tissues immediately adjacent to the left anterior descending artery. The left ventricle receives minor projections from the right A-V groove with major projections from subepicardial tissues along the left anterior descending artery. In some animals there also exists a definite left ventricular supply from the region of the left A-V groove. Whereas the thoracic vagi send dense projections to the atria, and particularly to nodal tissue, they also supply both ventricles with inhibitory and augmentor fibers. Although isolated cardiac nerves may carry predominantly sympathetic or parasympathetic fibers, many show rich intermingling of these fibers in trunks distal to the caudal cervical ganglion.ADDITIONAL KEY WORDS epicardium epicardial innervation epicardial denervation myocardial contractile force dogs • Considerable new information has recently been acquired concerning the sympathetic innervation of the heart by electrical stimulation of the stellate ganglion, its ansal connections to the caudal cervical ganglion, and individual cardiac nerves passing to the From the

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Background Cancer patients with acute venous thromboembolism (VTE) receiving anticoagulant treatment have an increased bleeding risk. Objectives We performed a prespecified secondary analysis of the randomized, open-label, Phase III CATCH trial (NCT01130025) to assess the rate and sites of and the risk factors for clinically relevant bleeding (CRB). Patients/Methods Patients with active cancer and acute, symptomatic VTE received either tinzaparin 175 IU kg once daily or warfarin (target International Normalized Ratio [INR] of 2.0-3.0) for 6 months. Fisher's exact test was used to screen prespecified clinical risk factors; those identified as being significantly associated with an increased risk of CRB then underwent competing risk regression analysis of time to first CRB. Results Among 900 randomized patients, 138 (15.3%) had 180 CRB events. CRB occurred in 60 patients (81 events) in the tinzaparin group and in 78 patients (99 events) in the warfarin group (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.45-0.89). Common bleeding sites were gastrointestinal (36.7%; n = 66), genitourinary (22.8%; n = 41), and nasal (10.0%; n = 18). In multivariate analysis, the risk of CRB increased with age > 75 years (HR 1.83, 95% CI 1.14-2.94) and intracranial malignancy (HR 1.97, 95% CI 1.07-3.62). In the warfarin group, 40.4% of CRB events occurred in patients with with an INR of < 3.0. A lower time in therapeutic range was associated with a higher risk of CRB. Conclusions CRB is a frequent complication in cancer patients with VTE during anticoagulant treatment, and is associated with age > 75 years and intracranial malignancy.

Myocardial contractile force was recorded at three to five positions on the canine heart while progressively more distal portions of the cardiac sympathetic nerves were electrically stimulated. When the electrodes were applied directly to the stellate ganglion or to the ansa subclavia, positive inotropic responses were generally observed on all of the test regions of the heart. However, when more distal branches of the cardiac nerves were stimulated, individual test regions were successively deleted from the general response. By carefully removing narrow strips of epicardium (epicardial denervation) from different portions of the heart, similar deletions in response were observed. These observations indicate that the peripheral autonomic innervation of the heart is distributed to circumscribed regions of cardiac musculature. Contractile segments of a given region of the heart may be organized in series and each component of the chain influences the contraction of neighboring elements, normally innervated segments mechanically interacting with noninnervated regions. Individual units of cardiac muscle may be markedly influenced through local intervention by the sympathetic nerve supply.

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