Resuscitation research has focused primarily on the initial stage of cardiac resuscitation and options by which a viable rhythm and spontaneous circulation could be restored. Less well defined, however, is the metabolic and mechanical fate of the myocardium after cardiac arrest has been reversed. The current proposal addresses these two stages of cardiac resuscitation with special focus on pharmacological interventions. The goal is to define the rationale, indication, timing and sequencing of vasopressor/inotropic and buffer therapy and to understand their potential interactions. A sequence of experiments would be performed on an established porcine model of cardiac arrest in which resuscitation would be attempted by conventional closed-chest methods. Myocardial blood blow in conjunction with coronary arteriovenous 02, C02, and lactate gradients and direct measurement of myocardial PO2, (H+), PC02 would serve as measures of altered myocardial metabolism and especially of ischemia. Myocardial PC02 would also serve as a marker of the severity and prognosis of myocardial ischemia. Left ventricular pressure-volume measurements, utilizing the conductance method, would provide indices of myocardial contractility, relaxation and compliance.
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