Regional Blood Flow Distribution During the Cushing Response: Alterations with Adrenergic Blockade.

The Cushing response is a systemic arterial hypertension exceeding an imposed intracranial pressure (ICP). This study was designed to test the hypothesis that the Cushing response is a balanced response in which a beta adrenergic cardiac component helps maintain cardiac output (CO) relatively constant in the face of an alpha receptor mediated peripheral vasoconstriction which raises arterial pressure. To test this hypothesis, regional blood flow distribution (radioactive microspheres) and CO (thermal dilution) were measured during the Cushing response under unblocked, beta receptor blocked (2 mg/kg propranolol), and alpha receptor blocked (0.5 mg/kg + 0.5 mg/kg/min phentolamine) conditions in chloralose anesthetized dogs. The Cushing response was generated by increasing ICP to 150 mmHg by the infusion of temperature controlled artificial cerebrospinal fluid into the cisterna magna. During the Cushing response in unblocked animals, cerebral blood flow (CBF) decreased to 50% of control, coronary blood flow increased to 220% of control, and peripheral tissue blood flow was reduced only in the kidneys (18%) and the intestines (small = 22%, large = 35%). There were no significant changes in blood flow to the esophagus, stomach, liver, pancreas, spleen, skin, and skeletal muscle. CO and heart rate (HR) decreased (16% and 38%, respectively) and total peripheral resistance (TPR) and stroke volume (SV) increased (68% and 38%, respectively) during an unblocked Cushing response. During a beta blocked Cushing response, CBF again decreased to 50% of control. However, coronary blood flow decreased slightly (20%), and peripheral tissue blood flows were profoundly reduced (40-80%) in all tissues. CO and HR were markedly reduced (69% and 62%, respectively), TPR increased four fold (to 466% of control), and SV was unchanged during a beta blocked Cushing response. During an increase in ICP under alpha blockade, a Cushing response could not be sustained. CBF decreased to less than 10% of control, coronary blood flow increased to 350% of control, and peripheral tissue blood flows, HR, and SV were in general unchanged. CO increased to 155% of control and TPR decreased to 67% of control. We conclude that the Cushing response in the intact animal combines a peripheral component (alpha receptor mediated peripheral vasoconstriction) which is the primary driving force raising arterial pressure with a cardiac component (beta adrenergic stimulation) which maintains cardiac output relatively constant in the face of the systemic hypertension.Ph.D.Animal PhysiologyUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/159849/1/8402394.pd