Myocardial, coronary, and peripheral effects of xamoterol (ICI 118,587) in open-chest pigs.
The hemodynamic and coronary effects of increasing doses of xamoterol, a beta-adrenoceptor partial agonist, were assessed in an anesthetized pig preparation in which cardiovascular reflexes were abolished and sympathetic tone was modified by infusion of noradrenaline (NA). Xamoterol, in basal conditions, increased heart rate (HR) from 104 +/- 12 to 120 +/- 13 beats/min (p less than .001); systolic, diastolic, and mean blood pressure, respectively, from 77 +/- 8 to 103 +/- 17 mmHg (p less than .01), from 48 +/- 7 to 70 +/- 12 mmHg (p less than .01), and from 58 +/- 7 to 84 +/- 14 mmHg (p less than .01); left ventricular dP/dT max from 2098 +/- 564 to 4205 +/- 937 mmHg/sec (p less than .001); and systemic vascular resistance (SVR) from 1745 +/- 564 to 2270 +/- 739 dynes sec cm-5 (p less than .01). The increase in HR and dP/dT max brought about by xamoterol was about 37% and 56%, respectively, of the maximum increase produced by NA. At the highest level of sympathetic tone, xamoterol reduced HR from 148 +/- 11 to 122 +/- 11 beats/min (p less than .001) and no significant change was observed in dP/dT max. The increase in blood pressure and SVR induced by xamoterol was maintained at each level of sympathetic tone. On the contrary, SVR did not change after NA, as expected, since receptors were fully blocked. For a given inotropic effect, xamoterol and NA produced a similar increase in coronary blood flow and myocardial O2 consumption.(ABSTRACT TRUNCATED AT 250 WORDS)
Galiè
N
N
Institute of Cardiovascular Diseases, University of Bologna, Italy.
Metalli
M
M
Zannoli
R
R
Binetti
G
G
Branzi
A
A
Magnani
B
B
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000187:drug effects*; D007262:Infusions, Intravenous; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*; D012018:Reflex / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects*; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D017307:Xamoterol
D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D017307:Xamoterol; D009638:Norepinephrine