Previous work in the anesthetized dog has demonstrated that following coronary ligation in the chronically (2-3 weeks) sympathetomized heart, infarct size is dramatically less than in controls. This anti-infarction effect is not evident immediately after sympathectomy, but results strongly suggest that the action is attributable to time dependent reductions in both myocardial oxygen requirement and coronary collateral resistances. To further explore this effect and its underlying causes, the proposed work is an extension of 5 previously funded studies. Studies proposed are as follows: (1) Study 6 will use the nitro-blue tetrazolium method to examine the anti-infarction effect after longer periods of cardiac sympathectomy (4-12 weeks). The results will provide further insight into the time-dependency of the effect. (2) Study 7 will use retrograde flow techniques in the isolated heart to examine the changes in collateral resistances after longer periods of sympathectomy (4-12 weeks). If as previously suggested, the collateral circulation undergoes a structural development after sympathectomy, the changes in resistance should be progressive. (3) Study 8 will extend previous work to a more physiological preparation--the chronically instrumented conscious dog. Following 2-12 weeks of sympathectomy, changes in myocardial contractile function (LVP, uP/dP max, segmental shortening) and in collateral function (peripheral coronary pressure, microsphere perfusion) during 2-min coronary occlusions will be assessed in the conscious animal and compared to controls. (4) Study 9 will examine the effect of chronic sympathectomy (2-12 weeks) on myocardial oxygen and blood flow requirements in the conscious dog. At rest and during standardized exercise, indices of cardiac performance (LVP, dP/dt max, TTI, segmental shortening, heart rate, rate-pressure product) will be monitored and related to MVO2 and blood flow. The results of these studies will tremendously expand our understanding of the long-term effects of cardiac sympathectomy, especially during myocardial ischemic insult.
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