Intracarotid verapamil decreases both proximal and distal human cerebrovascular resistance.
BACKGROUND
The authors determined the segmental effects of intracarotid verapamil in human subjects by using a novel method of measuring proximal and distal cerebrovascular resistance. Their hypothesis was that intracarotid verapamil, a calcium channel-blocking drug that augments cerebral blood flow and reverses arterial spasm, would decrease both the proximal-conductance and the distal-arteriolar resistance.


METHODS
Coaxial catheters were transfemorally floated into internal carotid and middle cerebral arteries during cerebral angiography. Pressures were recorded in the femoral, internal carotid, and middle cerebral arteries. Hemispheric cerebral blood flow was measured by the intracarotid Xe injection technique. Cerebrovascular resistance was measured for the proximal and distal arteries. Cerebral blood flow and hemodynamic data were recorded during intracarotid infusion of saline and verapamil (1 mg/min) for 5 min. Transcranial Doppler blood flow velocity in the middle cerebral artery was also recorded.


RESULTS
Intracarotid verapamil increased in 133Xe cerebral blood flow from 43 +/- 11 to 59 +/- 11 ml.100 g(-1).min(-1) (P = 0.001; n = 9). The cerebrovascular resistance measured for the proximal and distal arteries decreased from 0.17 +/- 0.95 to 0.12 +/- 0.75 and from 1.63 +/- 0.78 to 1.03 +/- 0.33 mmHg.ml(-1).100 g(-1).min(-1) (P < 0.01), respectively. The calculated proximal-conductive and distal-arteriolar (pial plus parenchymal) resistances showed a similar decrease. Transcranial Doppler measurements (n = 5) underestimated the effects of intracarotid verapamil that were consistent with an increase in middle cerebral artery diameter.


CONCLUSIONS
Intracarotid verapamil decreases both the proximal-conductance and the distal-arteriolar resistance. Furthermore, it is feasible to investigate segmental effects of drugs in human subjects by measuring changes in pressure gradients within the cerebral arteries and simultaneous Xe cerebral blood flow measurements.
Joshi
Shailendra
S
Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA. sj121@columbia.edu
Meyers
Philip M
PM
Pile-Spellman
John
J
Wang
Mei
M
Sahlein
Daniel H
DH
D000328:Adult; D002339:Carotid Arteries / Q000187:drug effects; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D014655:Vascular Resistance / Q000187:drug effects*; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology*; D014980:Xenon Radioisotopes
D014980:Xenon Radioisotopes; D014700:Verapamil