Algogenic effects of the proximal and distal intracoronary infusion of adenosine. Pathophysiologic implications on the mechanisms of ischemic cardiac pain.
BACKGROUND
It has been hypothesized that ischemic cardiac pain might be due to a spatially restricted intense stimulation of non-specific cardiac receptors. If this hypothesis is correct a strong stimulation with an adequate stimulus of a limited myocardial region should cause more pain than a weaker stimulation of a larger myocardial region.


METHODS
To test this hypothesis, we carried out a systematic study in 8 male patients (mean age 52 +/- 9 years) with uncomplicated stable angina pectoris and significant isolated proximal left anterior descending coronary artery stenosis in whom the same amount of adenosine, a known mediator of cardiac and muscular ischemic pain, was infused at the proximal and distal site of the left anterior descending coronary artery. Increasing doubling doses (from 108 to 3456 micrograms/min) or adenosine were infused for periods of 2 min each into the left anterior descending coronary artery through a 2.8 F catheter. Adenosine was infused in each patient both proximally to the first diagonal branch and distally to the last diagonal branch of the left anterior descending coronary artery. The initial infusion site, proximal or distal, was randomized. At the beginning of the study patients were asked to promptly report the onset of pain. Time to onset of adenosine-induced pain and maximal pain severity (assessed by a visual analog scale) were recorded. Twelve electrocardiographic leads were recorded throughout the study.


RESULTS
Seven patients experienced pain during adenosine infusion both at the proximal and distal level. One patient experienced pain only during adenosine infusion at the proximal site. In all patients pain occurred earlier (176 +/- 125 vs 343 +/- 207 s, p = 0.005) and its severity was greater (51 mm, range 20-95, vs 27 mm, range 0-69, p = 0.002) during infusion at the proximal site. No patient exhibited electrocardiographic changes during the study.


CONCLUSIONS
Adenosine infusion at a proximal coronary site causes pain which occurs earlier and is more severe than that experienced during its infusion at a distal site. These findings suggest that the intensity of ischemic cardiac pain is determined by the number of stimulated receptors rather than by the intensity of their stimulation.
Crea
F
F
Istituto di Cardiologia, Università Cattolica del Sacro Cuore, Roma. f.crea@flashnet.it
Gaspardone
A
A
Versaci
F
F
Tomai
F
F
Perino
M
M
Chiariello
L
L
Gioffré
P A
PA
D000241:Adenosine / Q000008:administration & dosage*; D000328:Adult; D000787:Angina Pectoris / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D015906:Angioplasty, Balloon, Coronary; D003327:Coronary Disease / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D003331:Coronary Vessels; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D010147:Pain Measurement; D013997:Time Factors
D000241:Adenosine