ALBERT

Notes: Abstract Currently, considerable clinical interest exists in the vasoactivity of large coronary arteries due to the prevalence of coronary vasospasm in mediating angina pectoris and even myocardial infarction. Although arterial elastic properties have been studied extensively in acute, anesthetized animal experiments and in vitro preparations, few data are available on these properties in conscious, chronically instrumented animals, where the complicating influences of anesthesia, recent surgery, and acute manipulation of the vessel are minimized. To study vascular smooth muscle in the conscious animal we modified the transit-time dimension measurement technique by designing smaller, higher frequency (7 MHz) transducers, and introducing electronic refinements to accurately measure smaller dimensions (2 mm minimum). We applied this technique to the left circumflex coronary (LCC) artery, along with arterial pressure measurements from either chronically implantable strain-gauge manometers, or microtip catheter manometers, to study dynamic compliance and vascular control mechanisms of these arteries for periods of months in conscious, chronically instrumented animals. Infusion of an α-adrenergic vasoconstrictor, methoxamine (50 μg/kg/min), caused sustained reduction in LCC diameter (9%±2%) at a time when mean arterial pressure rose by 65%±5% and heart rate and mean coronary blood flow (electromagnetic flow probe) were returned to control levels. Methoxamine induced a marked leftward shift in the pressure-diameter and stress-radius relationships, reducing vascular caliber for any given stress and pressure level. Moreover, smooth-muscle activation raised the effective incremental modulus (Einc) of the coronary arterial wall when compared at similar radii, but it reduced Einc when compared at similar stress or pressure levels. Thus, for any given arterial pressure level the Einc of the LCC artery wall can be reduced considerably by the enhanced smooth-muscle activation elicited by methoxamine. Nitroglycerin (25 μg/kg) induced an initial decrease in LCC diameter as pressure fell and LCC blood flow rose. However, dimensions then increased, reaching a maximum 5 minutes later, when LCC blood flow was reduced, and heart rate and left ventricular dP/dt were at control levels. The calcium-channel antagonist, nifedipine, caused similar early changes, with the increase in LCC caliber persisting for 46±5 minutes while LCC blood flow returned to control in 15±3 minutes. Thus the long-lasting effects on large coronary arteries induced by nitroglycerin and calcium channel blockers are particularly important therapeutically, compared to the less persistent effects upon the coronary resistance vessels. The results of these experiments demonstrate (1) that the direct and continuous measurement of arterial diameter provides a sensitive and illuminating technique for the study of vascular smooth muscle activity, and (2), that although the technique is potentially applicable to acute animal studies, its real utility lies in the area of chronically instrumented animals where the many complicating influences of acute experimental preparations are eliminated or minimized.